Katie was getting nervous.

At 16, she was the only one in her group of friends who had not started
Page 296 menstruating. Katie had always dreamed of having three beautiful children someday and she was worried. Her
mother took her to see Dr. Josephine, who ordered several blood tests. When the results came back, Dr.
Josephine gently explained to Katie and her mother that Katie would never be able to have children and would
CHAPTER never menstruate. Dr. Josephine then asked Katie to wait in the outer room while she spoke privately to her

10
mother. She explained to Katie’s mom that Katie had Androgen Insensitivity Syndrome. Though Katie was
genetically male and her gonads produced more of the male reproductive hormone, testosterone, than the
female reproductive hormone, estrogen, Katie did not reflect the tissue changes expected.

Endocrine System
What malfunction in Katie’s body would cause this? Why does Katie’s body look feminine if she is
genetically male?

Answers to this question and the chapter’s odd-numbered Apply It questions can be found in Appendix E.

Module 8 Endocrine System

10.1 PRINCIPLES OF CHEMICAL COMMUNICATION

Learning Outcomes After reading this section, you should be able to

A. Describe the four classes of chemical messengers.

B. Define hormone and target tissue.
C. Distinguish between endocrine and exocrine glands.

Characteristics of the Endocrine System

The endocrine system is composed of endocrine glands and specialized

endocrine cells located throughout the body (figure 10.1). Endocrine glands and
cells secrete very small amounts of chemical messengers called hormones
(HOR-mohns; to excite) into the extracellular fluid. The hormones diffuse into
the blood to be transported to their target. Hormones circulate through the
bloodstream to specific sites called target tissues or effectors. At their target
tissues, hormones stimulate a specific response. Thus, the term endocrine (EN-
doh-krin) —derived from the Greek words endo, meaning “within,” and krino, “to
secrete”—appropriately describes this system.

The endocrine s ys tem is es s ential for the body to m aintain hom eos tas is .

Page 297

LEARN TO APPLY IT
 of the chemical messenger and its mode of transport in the body (table 10.1). In
this section, we describe chemical messengers in terms of how they function. But
it is important to note that some chemical messengers fall into more than one
functional category. For example, prostaglandins are listed in multiple categories
because they have diverse functions and cannot be categorized in just one class.
Therefore, the study of the endocrine system includes several of the following
categories:

1. Autocrine chemical messengers. An autocrine (auto-, self) chemical messenger

stimulates the cell that originally secreted it. Good examples of autocrine chemical
messengers are those secreted by white blood cells during an infection. Several types of
white blood cells can stimulate their own replication so that the total number of white
blood cells increases rapidly (see chapter 14).
2. Paracrine chemical messengers. Paracrine (para-, next to) chemical messengers act
locally on neighboring cells. These chemical messengers are secreted by one cell type
into the extracellular fluid and affect surrounding cells. An example of a paracrine
chemical messenger is histamine, released by certain white blood cells during allergic
reactions. Histamine stimulates vasodilation in nearby blood vessels.
Figure 10.1 Major Endocrine Glands and Their Locat ions
Th e m ajor endocr ine glands ar e: pineal gland, pitu itar y , th y r oid, par ath y r oids, th y m u s, adr enals, pancr eas,
3. Neurotransmitters. Neurotransmitters are chemical messengers secreted by neurons that
ov ar ies, and testes. activate an adjacent cell, whether it is another neuron, a muscle cell, or a glandular cell.
Neurotransmitters are secreted into a synaptic cleft, rather than into the bloodstream
Endocrine glands are not to be confused with exocrine glands. Exocrine glands (see chapter 8). Therefore, in the strictest sense neurotransmitters are paracrine
have ducts that carry their secretions to the outside of the body, or into a hollow chemical messengers, but for our purposes it is most appropriate to consider them as a
organ, such as the stomach or intestines. Examples of exocrine secretions are separate category.
saliva, sweat, breast milk, and digestive enzymes.
4. Endocrine chemical messengers. Endocrine (endo-, within) chemical messengers are
The study of the endocrine system, known as endocrinolog, is the topic of this secreted into the bloodstream by certain glands and cells, which together constitute the
chapter. In this chapter, we present the general principles of hormones and we endocrine system. These chemical messengers travel through the blood to their target
discuss specific hormones and their functions. Hormones have a role in most cells.
physiological processes in the body.
Page 298
Classes of Chemical Messengers
TABLE 10.1 Classes of Chemical Messengers
The body has a remarkable capacity for maintaining homeostasis despite having to
Chemical
coordinate the activities of nearly 40 trillion cells. The principal means by which Messenger Description Example
this coordination occurs is through chemical messengers, some produced by the
Autocrine Secreted by Eicosanoids
nervous system and others produced by the endocrine system. Chemical cells in a local (prostaglandins,
messengers allow cells to communicate with each other to regulate body area; thromboxanes,
activities. influences the prostacyclins,
activity of the leukotrienes)
Most chemical messengers are produced by a specific collection of cells or by a same cell or
gland. Recall from chapter 4 that a gland is an organ consisting of epithelial cells cell type from
that specialize in secretion, which is the controlled release of chemicals from a which it was
secreted
cell. This text identifies four classes of chemical messengers based on the source
 Chemical many disorders of the body are caused by either hypersecretion or hyposecretion
Messenger Description Example of hormones.
Paracrine Produced by Somatostatin, The main regulatory functions of the endocrine system are the following:
a wide variety histamine,
of tissues eicosanoids 1. Regulation of metabolism. Controls the rate of nutrient utilization and energy
and secreted
into
production.
extracellular Page 299
fluid; has a
localized
2. Control of food intake and digestion. Regulates the level of satiation (fullness) and the
effect on breakdown of food into individual nutrients.
other tissues
3. Modulation of tissue development. Influences the development of tissues, such as those
Neurotransmitter Produced by Acetylcholine,
neurons; epinephrine
of the nervous system.
secreted into 4. Regulation of ion levels. Helps monitor blood pH, as well as Na+, K+, and Ca2+
a synaptic
cleft by concentrations in the blood.
presynaptic 5. Control of water balance. Regulates water balance by controlling the solute
nerve
terminals; concentration of the blood as well as controlling membrane permeability.
travels short 6. Regulation of cardiovascular functions. Helps regulate the heart rate and blood
distances;
influences pressure and prepare the body for physical activity.
postsynaptic
cells
7. Control of blood glucose and other nutrients. Regulates the levels of glucose and other
nutrients in the blood.
Endocrine Secreted into Thyroid
the blood by hormones, 8. Control of reproductive functions. Controls the development and functions of the
specialized growth
cells; travels hormone, insulin,
reproductive systems in males and females.
some epinephrine, 9. Stimulation of uterine contractions and milk release. Regulates uterine contractions
distance to estrogen,
target tissues; progesterone,
during delivery and stimulates milk release from the breasts in lactating females.
results in testosterone, 10. Modulation of immune system function. Helps control the production of immune cells.
coordinated prostaglandins
regulation of
cell function 10.3 HORMONES

Learning Outcomes After reading this section, you should be able to

10.2 FUNCTIONS OF THE ENDOCRINE SYSTEM
A. Describe the common characteristics of all hormones.
Learning Outcomes After reading this section, you should be able to B. List and describe the two chemical categories of hormones.
C. Explain the influence of the chemical nature of a hormone on its transport in the blood, its removal from the
A. Explain the types of information that are necessary to understand endocrine function. blood, and its life span.
B. Describe the ten regulatory functions of the endocrine system. D. Describe the three main patterns of hormone secretion.

The endocrine system is one of the two important control systems of the body. The word hormone is derived from the Greek word hormon, which means to “set
The nervous system is the body’s other important control system (see figure 10.1). into motion.” Hormones are very powerful molecules.
Hormones of the endocrine system are secreted in response to humoral, neural, or
hormonal stimuli to regulate homeostasis. In order to understand completely how Chemical Nature of Hormones
the endocrine system regulates body functions, you need to know the various
Hormones fit into one of two chemical categories: (1) lipid-soluble hormones and
endocrine glands, their hormones, and their mechanisms of action. In addition,
(2) water-soluble hormones, a distinction based on their chemical composition,
which influences their chemical behavior. Recall from chapter 3 that the cell
membrane is a selectively permeable phospholipid bilayer that excludes most
water-soluble molecules but allows lipid-soluble molecules to pass through.
Therefore, the entire basis of a hormone’s metabolism—its transport in the blood,
its interaction with its target, and its removal from the body—is dependent on the
hormone’s chemical nature.
Within the two chemical categories, hormones can be subdivided into groups
based on their chemical structures. Steroid hormones are those derived from
cholesterol, thyroid hormones are derived from the amino acid tyrosine, and other
hormones are categorized as amino acid derivatives, peptides, or proteins.

Lipid-Soluble Hormones
Lipid-soluble hormones are nonpolar, and include steroid hormones, thyroid
hormones, and fatty acid derivative hormones, such as certain eicosanoids.

Transport of Lipid-Soluble Hormones

Because of their small size and low solubility in aqueous fluids, if lipid-soluble
hormone molecules circulated in the blood unprotected, they could be easily Figure 10.2 Effect s of Binding Prot eins
removed from the blood and would be unable to effectively regulate their targets. Fr ee h or m ones (th ose th at cir cu late fr eely in th e blood) im m ediately activ ate tar get cells once th ey ar e deliv er ed
fr om th e blood. Th e blood lev els of th ese h or m ones tend to flu ctu ate to a gr eater degr ee th an th e lev els of
There are at least three mechanisms that could potentially result in the removal of h or m ones th at attach to binding pr oteins. Water -solu ble h or m ones th en bind to th eir r eceptor s, w h ich ar e
unprotected lipid-soluble hormones from the body: (1) breakdown by enzymes in m em br ane-bou nd in th e tar get cell. Hor m ones th at ar e tr anspor ted in th e blood attach ed to binding pr oteins
cir cu late in th e blood as bou nd or fr ee h or m ones. A s th e concentr ation of fr ee h or m ones decr eases, bou nd
the liver or enzymes in the lungs, (2) excretion into urine by the kidneys, and (3) h or m ones ar e r eleased fr om th e binding pr oteins. Th is pr ov ides a ch r onic, stable su pply of h or m ones and, th u s,
breakdown by enzymes in the bloodstream. Hormones that are degraded by m or e-consistent contr ol of tar get cells. Th is is especially im por tant for h or m ones th at r egu late basal m etabolism .
enzymes in the blood would then be excreted in the urine or in bile produced in Lipid-solu ble h or m ones bind th eir r eceptor s in eith er th e cy toplasm or th e nu cleu s.

the liver.
Water-Soluble Hormones
Fortunately, lipid-soluble hormones are not unprotected. Instead, they travel in
the bloodstream bound to binding proteins (figure 10.2). Binding proteins Water-soluble hormones are polar molecules; they include protein hormones,
“chaperone” the hormone. This binding significantly reduces the rate at which peptide hormones, and most amino acid derivative hormones.
lipid-soluble hormones are degraded or removed from the blood. The life span of
lipid-soluble hormones in the blood typically ranges from a few days to several Transport of Water-Soluble Hormones
weeks. Eventually, even though lipid-soluble hormones are bound to binding Because water-soluble hormones can dissolve in blood, many circulate as free
proteins, they are still removed from the plasma through excretion in urine from hormones, meaning that most of them dissolve directly into the blood and are
the kidney or bile from the liver (bile enters the digestive tract). delivered to their target tissue without attaching to a binding protein (see figure
10.2). Because many water-soluble hormones are quite large, they do not readily
Page 300 diffuse through the walls of all capillaries; therefore, they tend to diffuse from the
blood into tissue spaces more slowly. Organs regulated by some protein hormones
have very porous, or fenestrated, capillaries to aid in delivery of these hormones
to individual cells (see chapter 13). On the other hand, other water-soluble
hormones are quite small and are attached to a binding protein to avoid being
filtered out of the blood.
All hormones are destroyed either in the blood or at their target cells. The
destruction and elimination of hormones limit the length of time they are active,
and body processes change quickly when hormones are secreted and remain include elevated blood glucose levels directly stimulating the pancreas to secrete
functional for only short periods. the hormone insulin, and elevated blood potassium levels directly stimulating the
The water-soluble hormones have relatively short half-lives because they are adrenal cortex to secrete the hormone aldosterone.
rapidly broken down by enzymes within the bloodstream. The kidneys then
remove the hormone breakdown products from the blood. Target cells can also Page 301
destroy water-soluble hormones. Once the hormones are inside the target cell,
lysosomal enzymes degrade them. Often the target cell recycles the amino acids of
peptide and protein hormones and uses them to synthesize new proteins. Thus,
hormones with short half-lives normally have concentrations that change rapidly
within the blood and tend to regulate activities that have a rapid onset and short
duration.
However, some water-soluble hormones are more stable in the blood than
others. There are many modifications made to hormone molecules that help
protect them from being destroyed. Three important modifications include:

1. Having a carbohydrate attached to them.

2. Having a terminal end protected from protease activity.
3. Having binding proteins. Bound hormones circulate in the plasma longer than free
water-soluble hormones do.

10.4 CONTROL OF HORMONE SECRETION

Figure 10.3 Humoral Regulat ion of Hormone Secret ion
Learning Outcomes After reading this section, you should be able to Som e h or m ones ar e r eleased w h en th e blood lev els of a cer tain ch em ical ch anges. For exam ple, if blood Ca 2+ lev els
decr ease, PTH is secr eted. If blood Ca 2+ lev els incr ease, PTH secr etion slow s. Som e h or m ones ar e secr eted in dir ect
A. List and describe the three stimulatory influences on hormone secretion and give examples. r esponse to ch anges in cer tain blood-bor ne ch em icals, su ch as Ca 2+.
B. List and describe the three inhibitory influences on hormone secretion and give examples.
C. Describe the major mechanisms that maintain blood hormone levels. Control by Neural Stimuli
The second type of hormone regulation involves neural stimuli of endocrine
Three types of stimuli regulate hormone release: (1) humoral, (2) neural, and (3) glands. Figure 10.4 illustrates the neural control of hormone secretion from cells
hormonal. No matter what stimulus causes the release of the hormone, however, of an endocrine gland.
the blood level of most hormones fluctuates within a homeostatic range through
negative-feedback mechanisms (see chapter 1). In a few instances, positive- Page 302
feedback systems also regulate blood hormone levels.
Stimulation of Hormone Release
PROCESS Figure
Control by Humoral Stimuli
Molecules and ions in the bloodstream can directly stimulate the release of some
hormones. These chemicals are referred to as humoral stimuli. The word
humoral refers to body fluids, including blood. The cells that secrete these
hormones have receptors for certain substances in the blood. For example,
calcium stimulates the release of the hormone PTH. Figure 10.3 illustrates that
when the blood level of a particular chemical changes (calcium), the hormone
(PTH) is released in response to the chemical’s concentration. Other examples
 Some neurons secrete chemical messengers directly into the blood when they
are stimulated, making these chemical messengers hormones, which are called
neuropeptides. Specialized neuropeptides stimulate hormone secretion from other
endocrine cells and are called releasing hormones, a term usually reserved for
hormones from the hypothalamus.

Control by Hormonal Stimuli

The third type of regulation uses hormonal stimuli. It occurs when a hormone
is secreted that, in turn, stimulates the secretion of other hormones. The most
common examples are hormones from the anterior pituitary gland, called tropic
(TROH-pik) hormones. Tropic hormones are hormones that stimulate the
secretion of another hormone. Figure 10.5 illustrates hormone secretion from the
hypothalamus and pituitary, which is regulated by hormonal stimuli.

PROCESS Figure

PROCESS Figure 10.4 Control of Hormone Secretion by Direct Neural

Innervation
Some hormone secretion is due to a stimulus from a neurotransmitter.

What cell membrane component must the endocrine cell

have, in order to respond to a neurotransmitter?

❶ Following action potentials, neurons release a neurotransmitter into the

synapse with the cells that produce the hormone.
❷ In some cases, the neurotransmitter stimulates the cells to increase hormone
secretion. PROCESS Figure 10.5 Hormonal Regulation of Hormone Secretion
For example, the sympathetic nervous system (see chapter 8) stimulates the Some hormone secretion is due to a stimulus from another hormone.
secretion of epinephrine and norepinephrine, from the adrenal gland during
exercise. Epinephrine and norepinephrine increase heart rate and, in turn,
increase blood flow through the exercising muscles. When the exercise stops, the
neural stimulation declines and the secretion of epinephrine and norepinephrine What type of hormonal secretion mechanism is found in
decreases. step 1?
❶ Neurons in the hypothalamus release stimulatory hormones, called releasing Negative Feedback
hormones. Releasing hormones travel in the blood to the anterior pituitary Most hormones are regulated by a negative-feedback mechanism, whereby the
gland. hormone’s secretion is inhibited by the hormone itself once blood levels have
❷ Releasing hormones stimulate the release of hormones from the anterior reached a certain point and there is adequate hormone to activate the target cell.
pituitary that travel in the blood to their target endocrine cell. The hormone may inhibit the action of other, stimulatory hormones to prevent
the secretion of the hormone in question. Thus, it is a self-limiting system.
❸ The target endocrine cell secretes its hormone into the blood, where it travels to For example, thyroid hormones inhibit the secretion of their releasing hormone
its target and produces a response. from the hypothalamus and their tropic hormone from the anterior pituitary.
The steps for the thyroid hormone negative-feedback system are shown in
Inhibition of Hormone Release
figure 10.6a.
Stimulating hormone secretion is important, but inhibiting hormone release is
also important. This process involves the same three types of stimuli: (1) humoral, Page 303
(2) neural, and (3) hormonal.

Inhibition of Hormone Release by Humoral Stimuli PROCESS Figure

Often when a hormone’s release is sensitive to the presence of a humoral
stimulus, there exists a companion hormone whose release is inhibited by the
same humoral stimulus. Usually, the companion hormone’s effects oppose those
of the secreted hormone and counteract the secreted hormone’s action. For
example, to raise blood pressure, the adrenal cortex secretes the hormone
aldosterone in response to low blood pressure. However, if blood pressure goes
up, the atria of the heart secrete the hormone atrial natriuretic peptide (ANP),
which lowers blood pressure. Therefore, aldosterone and ANP work together to
maintain homeostasis of blood pressure.

Inhibition of Hormone Release by Neural Stimuli

Neurons inhibit targets just as often as they stimulate targets. If the
neurotransmitter is inhibitory, the target endocrine gland does not secrete its
hormone.
PROCESS Figure 10.6 Negative and Positive Feedback
Inhibition of Hormone Release by Hormonal Stimuli Blood hormone levels are tightly regulated through negative and positive feedback.
Some hormones prevent the secretion of other hormones, which is a common
mode of hormone regulation. For example, hormones from the hypothalamus that
prevent the secretion of tropic hormones from the anterior pituitary gland are
called inhibiting hormones. Thyroid hormones can control their own blood What provides a negative feedback signal for a hormone
levels by inhibiting their anterior pituitary tropic hormone. Without the original that is regulated by a humoral stimulus? Explain.
stimulus, less thyroid hormone is released.
❶ The anterior pituitary gland secretes a tropic hormone, which travels in the
Regulation of Hormone Levels in the Blood blood to the target endocrine cell.
Two major mechanisms maintain hormone levels in the blood within a ❷ The hormone from the target endocrine cell travels to its target.
homeostatic range: (1) negative feedback and (2) positive feedback (see chapter 1).
❸ The hormone from the target endocrine cell also has a negative-feedback effect
on the anterior pituitary and hypothalamus, which decreases secretion of the
tropic hormone.

Positive Feedback
Some hormones, when stimulated by a tropic hormone, promote the synthesis
and secretion of the tropic hormone in addition to stimulating their target cell. In
turn, this stimulates further secretion of the original hormone. Thus, it is a self-
propagating system.
For example, prolonged estrogen stimulation promotes a release of the anterior
pituitary hormone responsible for stimulating ovulation.
The steps in the estrogen positive-feedback mechanism are shown in figure
10.6b.
❶ The anterior pituitary gland secretes a tropic hormone, which travels in the
blood to the target endocrine cell.
❷ The hormone from the target endocrine cell travels to its target.
Figure 10.7 Target Tissue Specificit y and Response
❸ The hormone from the target endocrine cell also has a positive-feedback effect Hor m ones bind to r eceptor pr oteins. Th e sh ape and ch em ical natu r e of each r eceptor site allow only a specific
h or m one to bind. Th is r elationsh ip is called specificity . A dditionally , in or der for a tar get cell to r espond to its
on the anterior pituitary, which increases the secretion of the tropic hormone. h or m one, th e h or m one m u st bind to its r eceptor .

10.5 HORMONE RECEPTORS AND MECHANISMS OF ACTION Classes of Receptors

Learning Outcomes After reading this section, you should be able to Lipid-soluble and water-soluble hormones bind to their own classes of receptors.
A. Describe the general properties of a receptor.
Figure 10.8 provides an overview of receptor type and mechanism of action.
B. Explain the mechanisms of action for the two types of receptor classes.
Page 304
C. Define amplification, and explain how, despite small hormone concentrations, water-soluble hormones can
cause rapid responses.

Hormones exert their actions by binding to target cell proteins called receptors.
A hormone can stimulate only the cells that have the receptor for that hormone.
The portion of each receptor molecule where a hormone binds is called a
receptor site, and the shape and chemical characteristics of each receptor site
allow only a specific type of hormone to bind to it. The tendency for each type of
hormone to bind to one type of receptor, and not to others, is called specificity
(figure 10.7). For example, insulin binds to insulin receptors, but not to receptors
for thyroid hormones. However, some hormones, such as epinephrine, can bind to
a “family” of receptors that are structurally similar. Because hormone receptors
have a high affinity for the hormones that bind to them, only a small
concentration of a given hormone is needed to activate a significant number of its
receptors.
 soluble hormones enter their target cell, they bind to nuclear receptors, which are most
often found in the cell nucleus (figure 10.8a). Nuclear receptors can also be located in
the cytoplasm, but then move to the nucleus when activated. When hormones bind to
nuclear receptors, the hormone-receptor complex interacts with DNA in the nucleus or
with cellular enzymes to regulate the transcription of particular genes in the target
tissue, a process that takes several minutes to several hours. Thyroid hormones and
steroid hormones (testosterone, estrogen, progesterone, aldosterone, and cortisol)
generally bind to nuclear receptors.
In addition to modulating gene transcription, it is now recognized that lipid-soluble
hormones have rapid effects (less than 1 minute) on target cells. These effects are most
likely mediated through membrane-bound receptors (see next paragraph).
2. Water-soluble hormones bind to membrane-bound receptors. Water-soluble hormones
are polar molecules and cannot pass through the cell membrane. Instead, they interact
with membrane-bound receptors, which are proteins that extend across the cell
membrane, with their hormone-binding sites exposed on the cell membrane’s outer
surface (figure 10.8b). When a hormone binds to a receptor on the outside of the cell
membrane, the hormone-receptor complex initiates a response inside the cell. Hormones
that bind to membrane-bound receptors include proteins, peptides, some amino acid
derivatives, such as epinephrine and norepinephrine, and some lipid-soluble hormones.

Action of Nuclear Receptors

Primarily, lipid-soluble hormones stimulate protein synthesis.

Figure 10.9 details the mechanism of action at nuclear receptors.

Page 305

PROCESS Figure

Figure 10.8 General Comparison of Nuclear and Membrane-Bound Recept ors

(a) Lipid-soluble h or m ones diffu se th r ou gh th e cell m em br ane of its tar get cell and bind to a cy toplasm ic r eceptor
or a nu clear r eceptor . In th e nu cleu s, th e com bination of th e h or m one and th e r eceptor initiates pr otein
sy nth esis, descr ibed later in th is ch apter . (b) Water-soluble h or m ones bind to th e exter nal por tion of m em br ane-
bou nd r eceptor s, w h ich ar e integr al m em br ane pr oteins on its tar get cell.

1. Lipid-soluble hormones bind to nuclear receptors. Lipid-soluble hormones are

relatively small and are all nonpolar. Recall from chapter 3 that nonpolar molecules can
freely cross the cell membrane. However, certain lipid-soluble hormones, in particular
thyroid hormones, utilize membrane transporters to enter the target cell. Once lipid-
 ❹ When the hormone-receptor complex binds to the hormone-response element,
it regulates the transcription of specific messenger RNA (mRNA)
molecules.
❺ Newly formed mRNA molecules move to the cytoplasm of the cell, and bind to
ribosomes to be translated into specific proteins.
❻ The new proteins produce the cell’s response to the lipid-soluble hormone.
For example, testosterone stimulates the synthesis of proteins that are
responsible for male sexual characteristics, such as the formation of muscle mass
and the typical male body structure. The steroid hormone aldosterone affects its
target cells in the kidneys by stimulating the synthesis of proteins that increase
the rate of Na+ and K+ transport. The result is a reduction in the amount of Na+
and an increase in the amount of K+ lost in the urine. Other hormones that
produce responses through nuclear receptor mechanisms include thyroid
hormones and vitamin D.
Target cells that synthesize new protein molecules in response to hormonal
stimuli normally have a latent period of several hours between the time the
hormones bind to their receptors and the time responses are observed. During
this latent period, mRNA and new proteins are synthesized. Hormone-receptor
complexes are eventually degraded within the cell, limiting the length of time
hormones influence the cells’ activities, and the cells slowly return to their
previous functional states.

Membrane-Bound Receptors and Signal Amplification

Recall from chapter 3 that the cell membrane contains proteins, which are
PROCESS Figure 10.9 Nuclear Receptor Model embedded in the phospholipid bilayer. Membrane-bound receptors are types of
Lipid-soluble hormones stimulate protein synthesis in their target cells. membrane proteins. These receptors activate responses in two ways: (1) Some
receptors alter the activity of G proteins at the inner surface of the cell membrane;
(2) other receptors directly alter the activity of intracellular enzymes. These
intracellular pathways elicit specific responses in cells, including the production of
Based on the characteristics of lipid-soluble hormones, explain why anabolic
steroids can have numerous side effects. molecules called second messengers. A second messenger molecule is
produced inside a cell once a hormone or another chemical messenger binds to
❶ After lipid-soluble hormones enter their target cell they bind to their receptors. certain membrane-bound receptors.
In response to the hormone, the second messenger then activates specific
❷ Lipid-soluble hormones either bind to cytoplasmic receptors and travel to the cellular processes inside the cell. In some cases, this coordinated set of events is
nucleus or bind to nuclear receptors. referred to as a second-messenger system. For example, cyclic adenosine
❸ The hormone-receptor complex binds to DNA to produce new proteins. The monophosphate (cAMP) (the second messenger) is a common second messenger
receptors that bind to DNA have fingerlike projections that recognize and bind produced when a ligand binds to its receptor. Rather than the ligand (the first
to specific nucleotide sequences in the DNA called hormone-response messenger) entering the cell to directly activate a cellular process, the ligand
elements. The combination of the hormone and its receptor forms a stimulates cAMP (the second messenger) production. It is cAMP that then
transcription factor. stimulates the cellular process. This mechanism is usually employed by water-
soluble hormones that are unable to cross the target cell’s membrane. It has also
been demonstrated that some lipid-soluble hormones activate second messenger
systems, which is consistent with actions via membrane-bound receptors.
Certain stimulants, such as caffeine, work by increasing the levels of cAMP inside
target cells. Based on the process shown here, what is a possible mechanism for caffeine
Membrane-Bound Receptors That Activate Adenylate Cyclase-Coupled G stimulation?
Proteins
Many membrane-bound receptors produce responses through the action of G ❶ Before the hormone binds to its receptor, the G protein freely floats in the cell
proteins. G proteins consist of three subunits; from largest to smallest, they are membrane.
called (1) alpha (α), (2) beta (β), and (3) gamma (γ). The G proteins are so named
❷ After a hormone binds to the receptor on the outside of a cell, the receptor
because one of the subunits binds to guanine nucleotides. In the inactive state, a
changes shape and as a result, the receptor binds to a G protein. Guanine
guanine diphosphate (GDP) molecule is bound to the α subunit of each G protein.
triphosphate (GTP) binds to the α subunit, thereby activating it.
In the active state, guanine triphosphate (GTP) is bound to the α subunit. Figure
10.10 outlines the mechanism of action of membrane-bound receptors. ❸ The G proteins separate from the receptor, and the activated α subunit
separates from the β and γ subunits. The activated α subunits
Page 306 activate adenylate cyclase (a-DEN-i-late CY-klase), an enzyme that converts
ATP to cAMP.
❹ Cyclic AMP functions as a second messenger. For example, cAMP binds to
PROCESS Figure protein kinases and activates them. Protein kinases are enzymes that, in
turn, regulate the activity of other enzymes. Protein kinases can either
stimulate or inhibit the activity of the other enzyme.
❺ The amount of time cAMP is present to produce a response in a cell is limited.
An enzyme in the cytoplasm, called phosphodiesterase (FOS-foh-dy-ES-ter-
ase), breaks down cAMP to AMP. Once cAMP levels drop, the enzymes in the
cell are no longer stimulated.

Page 307

Cyclic AMP can elicit many different responses in the body because each cell type
possesses a unique set of enzymes. For example, the hormone glucagon binds to
receptors on the surface of liver cells, activating G proteins and causing an
increase in cAMP synthesis, which stimulates the activity of enzymes that break
down glycogen into glucose for release from liver cells (figure 10.10).

Signal Amplification
The rate and magnitude at which a hormone’s response is stimulated are
determined by its mechanism of action at the receptor. Nuclear receptors work by
activating protein synthesis, which for some hormones can take several hours.
However, hormones that stimulate the synthesis of second messengers can
PROCESS Figure 10.10 Membrane-Bound Receptors Activating G
produce an almost instantaneous response because the second messenger
Proteins to Increase the Synthesis of cAMP
influences existing enzymes. In other words, the response proteins are already
Some G proteins initiate a cellular response through production of a second messenger, cAMP.
present. Additionally, each receptor produces thousands of second messengers,
leading to a cascade effect and ultimately amplification of the hormonal signal.
With amplification, a single hormone activates many second messengers, each of
which activates enzymes that produce an enormous amount of final product reflected by the fact that pregnancy is a long-term process. Thus, it is important
(figure 10.11). The efficiency of this second-messenger amplification is virtually that our bodies have hormones that can function over differing time scales.
unparalleled in the body and can be thought of as an “army of molecules”
launching an offensive. In a war, the general gives the signal to attack, and
thousands of soldiers carry out the order. The general alone could not eliminate Apply It 1
thousands of enemies. Likewise, one hormone could not single-handedly produce A drug binds to a receptor and prevents target tissues from
millions of final products within a few seconds. However, with amplification, one responding to a hormone. It is known that the drug is lipid-soluble
and that it prevents the synthesis of messenger RNA. Explain how
hormone has an army of molecules working simultaneously to produce the final the hormone produces a response in its target tissue.
products.

10.6 ENDOCRINE GLANDS AND THEIR HORMONES

Learning Outcomes After reading this section, you should be able to

A. State the location of each of the endocrine glands in the body.

B. Describe how the hypothalamus regulates hormone secretion from the pituitary.
C. Describe how the pituitary gland regulates the secretion of hormones from other endocrine glands.
D. Choose a hormone and use it to explain how negative feedback results in homeostasis.
E. For each of the major hormones in the chapter, describe the endocrine gland from which it is secreted, its
target tissue, the response of the target tissue, and the means by which its secretion is regulated.
F. List the effects of hyper- and hyposecretion of the major hormones.

The endocrine system consists of ductless glands that secrete hormones into the
interstitial fluid (see figure 10.1). The hormones then enter the blood. Not
surprisingly, the organs in the body with the richest blood supply are endocrine
glands, such as the adrenal gland and the thyroid gland.
Some glands of the endocrine system perform functions in addition to hormone
secretion. For example, the endocrine part of the pancreas has cells that secrete
hormones, whereas the much larger exocrine portion of the pancreas secretes
digestive enzymes. Portions of the ovaries and testes secrete hormones, but other
parts of the ovaries and testes produce oocytes (female reproductive cells) or
sperm cells (male reproductive cells), respectively.
Figure 10.11 Cascade Effect
Th e com bination of a h or m one w ith a m em br ane-bou nd r eceptor activ ates sev er al G pr oteins. Th e G pr oteins, in
tu r n, activ ate m any inactiv e adeny late cy clase enzy m es, w h ich cau se th e sy nth esis of a lar ge nu m ber of cA MP
Pituitary and Hypothalamus
m olecu les. Th e lar ge nu m ber of cA MP m olecu les, in tu r n, activ ate m any inactiv e pr otein kinase enzy m es, w h ich
pr odu ce a r apid and am plified r esponse. The pituitary (pi-TOO-i-tair-ree) gland is also called the hypophysis (high-POF-
ih-sis; hypo, under + physis, growth). It is a small gland about the size of a pea
Both nuclear receptor and membrane-bound receptor hormone systems are (figure 10.12, top). It is housed in a depression of the sphenoid bone inferior to
effective, but each is more suited to one type of response than another. For the hypothalamus of the brain. The hypothalamus (high-poh-THAL-ah-muss;
example, the reason epinephrine is effective in a fight-or-flight situation is that it serves as a control center for the autonomic nervous system as well as the
can turn on the target cell responses within a few seconds. If running away from endocrine system. Recall from chapter 8 that the hypothalamus is a region of the
an immediate threat depended on producing new proteins, a process that can take diencephalon, located inferior to the thalamus. The pituitary gland lies posterior
several hours, many of us would have already perished. On the other hand, to the optic chiasm and is connected to the hypothalamus by a stalk called the
pregnancy maintenance is mediated by steroids, long-acting hormones, which is infundibulum (IN-fun-DIB-you-lum; a funnel). The pituitary gland is divided
into two parts: (1) The anterior pituitary is made up of epithelial cells derived
from the embryonic oral cavity; (2) the posterior pituitary is an extension of Figure 10.12 Pit uit ary Gland, It s Hormones, and Their Target Tissues

the brain and is composed of neurons. The hormones secreted from each lobe of (Top) Th e pea-sized pitu itar y gland lies infer ior to th e h y poth alam u s of th e br ain. Th e infu ndibu lu m connects th e
h y poth alam u s and th e pitu itar y gland. (Bottom) Hor m ones secr eted by th e poster ior pitu itar y ar e indicated by
the pituitary gland are listed in table 10.2. blue shading, and h or m ones secr eted by th e anter ior pitu itar y by peach shading.

Page 308 Page 309

Page 310

TABLE 10.2 Endocrine Glands, Hormones, and Their Target Tissues

Gland Hormone Target Tissue Response

Pituitary gland

Anterior Growth hormone Most tissues Increases gene

expression,
breakdown of
lipids, and
release of fatty
acids from cells;
increases blood
glucose levels

Thyroid-stimulating hormone Thyroid gland Increases thyroid

(TSH) hormone
secretion
(thyroxine and
triiodothyronine)

Adrenocorticotropic hormone Adrenal cortex Increases secretion

(ACTH) of glucocorticoid
hormones, such
as cortisol;
increases skin
pigmentation at
high
concentrations

Melanocyte-stimulating Melanocytes in Increases melanin

hormone (MSH) skin production in
melanocytes to
make skin
darker in color

Luteinizing hormone (LH) or Ovary in females, Promotes ovulation

interstitial cell–stimulating testis in males and progesterone
hormone (ICSH) production in
ovary; promotes
testosterone
synthesis and
support for
sperm cell
production in
testis
Gland Hormone Target Tissue Response Gland Hormone Target Tissue Response

Follicle-stimulating hormone Follicles in ovary Promotes follicle Parathyroid glands Parathyroid hormone Bone, kidney Increases rate of
(FSH) in females, maturation and bone breakdown
seminiferous estrogen by osteoclasts;
tubules in secretion in increases
males ovary; promotes vitamin D
sperm cell synthesis,
production in essential for
testis maintenance of
normal blood
Prolactin Ovary and Stimulates milk calcium levels
mammary production and
gland in prolongs Adrenal medulla Epinephrine mostly, some Heart, blood Increases cardiac
females, testis progesterone norepinephrine vessels, liver, output; increases
in males secretion adipocytes blood flow to
following skeletal muscles
ovulation and and heart;
during increases release
pregnancy in of glucose and
women; fatty acids into
increases blood; in
sensitivity to LH general, prepares
in males body for physical
activity
Posterior Antidiuretic hormone (ADH) Kidney Conserves water;
constricts blood Adrenal cortex Mineralocorticoids(aldosterone) Kidneys; to lesser Increase rate of
vessels degree, sodium transport
intestine and into body;
Oxytocin Uterus Increases uterine sweat glands increase rate of
Mammary gland contractions potassium
Increases milk excretion;
letdown from secondarily favor
mammary water retention
glands
Glucocorticoids (cortisol) Most tissues (e.g., Increase lipid and
Thyroid gland Thyroid hormones (thyroxine, Most cells of the Increase metabolic liver, fat, protein
triiodothyronine) body rates, essential skeletal breakdown;
for normal muscle, increase glucose
process of immune synthesis from
growth and tissues) amino acids;
maturation increase blood
nutrient levels;
Calcitonin Primarily bone Decreases rate of
inhibit
bone
inflammation
breakdown;
and immune
prevents large
response
increase in blood
Ca2 + levels Adrenal androgens Most tissues Insignificant in
following a meal males; increase
female sexual
drive, growth of
pubic and
axillary hair
Gland Hormone Target Tissue Response Hormones from the pituitary gland control the functions of many other glands
in the body, such as the ovaries, the testes, the thyroid gland, and the adrenal
Pancreas Insulin Especially liver, Increases uptake
skeletal and use of cortex (figure 10.12, bottom). The pituitary gland also secretes hormones that
muscle, glucose and influence growth, kidney function, birth, and milk production by the mammary
adipose tissue amino acids glands. Historically, the pituitary gland was known as the body’s master gland
Glucagon Primarily liver Increases because it controls the function of so many other glands. However, we now know
breakdown of that the hypothalamus controls the pituitary gland in two ways: (1) hormonal
glycogen and
release of control and (2) direct innervation.
glucose into the
circulatory Hypothalamic Control of the Anterior Pituitary
system
The anterior pituitary gland synthesizes hormones, whose secretion is under the
Reproductive organs control of the hypothalamus. Figure 10.13 outlines the relationship between the
Testosterone Most tissues Aids in sperm cell hypothalamus and the anterior pituitary.
production,
maintenance of
functional
Page 311
reproductive
organs,
secondary sex
characteristics, PROCESS Figure
sexual behavior

Ovaries Estrogens, progesterone Most tissues Aid in uterine and

mammary gland
development and
function,
external
genitalia
structure,
secondary sex
characteristics,
sexual behavior,
menstrual cycle

Uterus, ovaries, inflamed Prostaglandins Most tissues Mediate

tissues inflammatory
responses;
increase uterine
contractions and
ovulation

Thymus Thymosin Immune tissues Promotes immune

system
development and
function

Pineal gland Melatonin Among others, Inhibits secretion of

hypothalamus gonadotropin-
releasing
hormone,
thereby
inhibiting
reproduction
 PROCESS Figure 10.13 Hypothalamus and Anterior Pituitary
Secretion of hormones from the anterior pituitary is regulated by releasing and inhibiting hormones
from the hypothalamus.

Given that the anterior pituitary releases multiple hormones, how is it that a
particular hypothalamus-releasing hormone stimulates the secretion of a specific anterior
pituitary hormone?

❶ Neurons of the hypothalamus produce neuropeptides and secrete them into a

capillary bed in the hypothalamus. Stimuli within the nervous system regulate
the secretion of releasing hormones and inhibiting hormones (circles) from
neurons of the hypothalamus.
❷ Releasing hormones and inhibiting hormones pass through the
hypothalamohypophysial portal system to the anterior pituitary.
❸ Once the neuropeptides arrive at the anterior pituitary gland, they leave the
blood and bind to membrane-bound receptors involved with regulating
anterior pituitary hormone secretion. The capillary beds and veins that
transport the releasing and inhibiting hormones are called the
hypothalamic-pituitary portal system. The hypothalamic neuropeptides
function as either releasing hormones or inhibiting hormones. Each releasing
hormone stimulates the production and secretion of a specific hormone by the
anterior pituitary. Each inhibiting hormone reduces the production and
secretion of a specific hormone by the anterior pituitary.
PROCESS Figure 10.14 Hypothalamus and Posterior Pituitary
Secretion of hormones from the posterior pituitary is regulated by neural input.
❹ In response to releasing hormones, anterior pituitary hormones (squares)
travel in the blood to their target tissue, which in some cases, are other
endocrine glands.
Are the posterior pituitary hormones water-soluble or lipid-soluble hormones?
How do you know, based solely on their mode of storage?
Hypothalamic Control of the Posterior Pituitary
The posterior pituitary is a storage location for two hormones synthesized by ❶ Stimulation of neurons within the hypothalamus controls the secretion of the
special neurons in the hypothalamus. Figure 10.14 outlines the relationship posterior pituitary hormones.
between the hypothalamus and the posterior pituitary.
❷ Action potentials are conducted by axons of the hypothalamic neurons through
Page 312 the hypothalamohypophysial tract to the posterior pituitary. The axon endings
of neurons store hormones in the posterior pituitary.
❸ In the posterior pituitary gland, action potentials cause the release of hormones
PROCESS Figure (circles) from axon terminals into the circulatory system.
❹ The hormones pass through the circulatory system and influence the activity of
their target tissues.
Within the hypothalamus and pituitary, the nervous and endocrine systems are
closely interrelated. Emotions such as joy and anger, as well as chronic stress,
influence the endocrine system through the hypothalamus. Conversely, hormones inhibiting hormone inhibits its secretion. Most people have a rhythm of growth
of the endocrine system can influence the functions of the hypothalamus and hormone secretion, with daily peak levels occurring during deep sleep. Growth
other parts of the brain. hormone secretion also increases during periods of fasting and exercise. Blood
levels of growth hormone do not become significantly elevated during periods of
Page 313 rapid growth, although children tend to have somewhat higher blood levels of
growth hormone than do adults. In addition to growth hormone, genetics,
Hormones of the Anterior Pituitary nutrition, and reproductive hormones influence growth.
The anterior pituitary is regulated differently than the posterior pituitary because Part of the effect of growth hormone is influenced by a group of protein
its hormones are synthesized by cells in the anterior pituitary. hormones called insulin-like growth factors (IGFs), or somatomedins (SOH-
The hormones secreted from the anterior pituitary are proteins. They are mah-toh-MEE-dins). Growth hormone increases IGF secretion from tissues such
transported in the blood, have a life span measured in minutes, and bind to as the liver, and the IGF molecules bind to receptors on the cells of tissues such as
membrane-bound receptors on their target cells. For the most part, each hormone bone and cartilage, where they stimulate growth. The IGFs are similar in structure
is secreted by a separate cell type. to insulin and can bind, to some degree, to insulin receptors. Also, insulin, at high
Many hormones from the anterior pituitary gland are tropic hormones, which concentrations, can bind to IGF receptors.
stimulate the secretion of other hormones from the target tissues (see figure
10.5).

Growth Hormone Apply It 2

Growth hormone (GH) stimulates the growth of bones, muscles, and other Zach has a son who wants to be a basketball player. Zach knows
something about GH. He asked his son’s doctor if he would
organs by increasing gene expression. It also slows protein breakdown during prescribe some GH for his son, so that he can grow taller. What do
periods of food deprivation and favors lipid breakdown. you think the doctor tells Zach? Why?
Too little growth hormone secretion can result from abnormal development of
the pituitary gland. A young person suffering from a deficiency of growth Thyroid-Stimulating Hormone
hormone remains small, although normally proportioned, and is called a Thyroid-stimulating hormone (TSH) binds to membrane-bound receptors on
pituitary dwarf (dwawrf). This condition can be treated by administering growth cells of the thyroid gland and stimulates the secretion of thyroid hormone. TSH
hormone. Because GH is a protein, it is difficult to produce artificially using can also stimulate growth of the thyroid gland. Thus, when too much TSH is
conventional techniques. However, human genes for GH have been successfully secreted, the thyroid gland enlarges and secretes too much thyroid hormone.
introduced into bacteria using genetic engineering techniques. The gene in the When too little TSH is secreted, the thyroid gland decreases in size and secretes
bacteria causes GH synthesis, and the GH can be extracted from the medium in too little thyroid hormone. The rate of TSH secretion is regulated by a releasing
which the bacteria are grown. Thus, modern genetic engineering has provided a hormone from the hypothalamus.
source of human GH for people who produce inadequate quantities.
Adrenocorticotropic Hormone
Page 314 Adrenocorticotropic (ah-DREE-noh-KOR-tih-koh-TROH-pik) hormone
(ACTH) binds to membrane-bound receptors on cells of the adrenal cortex. ACTH
Excess growth hormone secretion can result from hormone-secreting tumors of
increases the secretion of a hormone from the adrenal cortex called cortisol
the pituitary gland. If excess growth hormone is present before bones finish
(KOR-tih-sol), also called hydrocortisone. ACTH is required to keep the adrenal
growing in length, exaggerated bone growth occurs. The person becomes
cortex from degenerating. ACTH molecules also bind to melanocytes in the skin
abnormally tall, a condition called giantism (JYE-an-tizm). If excess hormone is
and increase skin pigmentation (see chapter 5). One symptom of too much ACTH
secreted after growth in bone length is complete, growth continues in bone
secretion is darkening of the skin. The rate of ACTH secretion is increased by a
diameter only. As a result, the facial features and hands become abnormally large,
releasing hormone from the hypothalamus.
a condition called acromegaly (ak-roh-MEG-ah-lee).
The secretion of growth hormone is controlled by two hormones from the Gonadotropins
hypothalamus. A releasing hormone stimulates growth hormone secretion, and an
Gonadotropins (GOH-nad-oh-TROH-pins) bind to membrane-bound receptors
on the cells of the gonads (ovaries and testes). The gonadotropins regulate the Prolactin
growth, development, and functions of the gonads. The two major gonadotropins
are (1) luteinizing (LOO-tee-in-eye-zing) hormone (LH) and (2) follicle- Prolactin (proh-LAK-tin; pro, precursor + lact, milk) binds to membrane-bound
stimulating hormone (FSH). In females, LH stimulates ovulation. LH also receptors in cells of the breast, where it helps promote development of the breast
promotes the secretion of the reproductive hormones, estrogen and progesterone, during pregnancy and stimulates the production of milk following pregnancy. The
from the ovaries. In males, LH stimulates interstitial cells of the testes to secrete regulation of prolactin secretion is complex and may involve several substances
the reproductive hormone testosterone and FSH stimulates the development of released from the hypothalamus. However, the principal control is exerted by
follicles in the ovaries and sperm cells in the testes. Without LH and FSH, the dopamine, formerly called prolactin-inhibiting hormone. Prolactin is now thought
ovaries and testes decrease in size, no longer produce oocytes or sperm cells, and to play many roles in homeostasis, including regulation of the ion composition of
no longer secrete hormones. A single releasing hormone from the hypothalamus blood and immune function.
increases the secretion of both LH and FSH.
Melanocyte-Stimulating Hormone
Melanocyte-stimulating (MEL-an-oh-cyte) hormone (MSH) binds to
membrane-bound receptors on melanocytes and causes them to synthesize
melanin. The structure of MSH is similar to that of ACTH, and oversecretion of
either hormone causes the skin to darken. Regulation of MSH is not well
MICROBES IN YOUR BODY understood, but there appear to be two regulatory hormones from the
hypothalamus—one that increases MSH secretion and one that decreases it.
Hormonal Regulation of Nutrient Metabolism is Influenced by Gut Microbes
Hormones of the Posterior Pituitary
Obesity has increased at an alarming rate over the last three decades. It is estimated that over 150 billion
adults worldwide are overweight or obese. In the United States, 40% of adults are obese. As obesity rates Antidiuretic Hormone
have increased, so have the rates of obesity-related health conditions such as insulin resistance, diabetes, and
cardiovascular disease. Why this dramatic increase? There are two main reasons for obesity: diet/lifestyle and Antidiuretic (an-tee-die-you-RET-ik; anti, against + uresis, urine volume)
gut bacteria; it seems these two may be related. hormone (ADH) binds to membrane-bound receptors and increases water
The most familiar cause of obesity is diet and lifestyle. The “typical” Western diet consists of frequent large reabsorption by kidney tubules. This results in less water lost as urine. ADH can
meals high in refined grains, red meat, saturated fats, and sugary drinks. Combined with a reduction in
physical activity and less sleep for many Americans, the Western diet and lifestyle can lead to obesity and also cause blood vessels to constrict when released in large amounts.
poor health. Consequently, ADH is also called vasopressin (vay-soh-PRESS-in). Reduced ADH
However, could humans’ gut microbiota be just as responsible (or even more responsible) for obesity? release from the posterior pituitary results in large amounts of dilute urine.
Comparisons between the gut microbiota of lean versus obese individuals seem to suggest the possibility of
an important link between gut microbiota and our weight. The human gut, like other animals, is densely A lack of ADH secretion causes diabetes insipidus, which is the production of a
populated with microbiota. The majority (90%) of human gut bacteria fall into two groups: Firmicutes and large amount of dilute urine. The consequences of diabetes insipidus are not
Bacteroidetes. Lean people have more Bacteroidetes than Firmicutes, while the opposite is true for obese obvious until the condition becomes severe, producing many liters of urine each
people.
We now know that gut microbiota affect nutrient processing and absorption, hormonal regulation of day. The large urine volume is created by excess water loss from the blood, which
nutrient use by body cells, and even our hunger level. increases the concentration of the body fluids and causes the loss of important
Changes in gut microbiota alter the hormonal regulation of nutrient use. Inflammation-promoting effects of electrolytes, such as Ca2 + , Na+ , and K+ . The lack of ADH secretion may be familiar
an imbalanced gut microbiota is thought to induce obesity via promoting insulin resistance, a known
autoimmune malfunction. Normal gut microbiota metabolism is critical for secretion of several anti-hunger to some who have ever had alcohol to drink. The diuretic actions of alcohol are
hormones, and anti-depressive neurotransmitters and neurochemicals. Shifts in normal gut microbiota, as due to its inhibition of ADH secretion.
related to diet, may very well disrupt normal anti-hunger signals and gut permeability, leading to over-eating
and inflammation related to obesity.
Can gut microbiota in obese people be manipulated to cause them to become lean? Several possibilities
Oxytocin
exist, including the distinct possibility that prescribing antibiotics against bacteria associated with obesity Oxytocin (OK-see-TOH-sin; swift birth) binds to membrane-bound receptors and
could shift the metabolism of an obese person to become leaner. Another possibility is the use of prebiotics—
causes contraction of the smooth muscle cells of the uterus as well as milk
nondigestible sugars that enhance the growth of beneficial microbiota. Finally, probiotic use is another
possible intervention for obesity. Probiotics are nonpathogenic live bacteria that confer a health benefit to the letdown from the breasts in lactating women. Commercial preparations of
host. This is a rapidly expanding field that holds much promise, but it is still in its beginning stages of our
understanding.
oxytocin, known as Pitocin, are given under certain conditions to assist in The thyroid gland contains numerous thyroid follicles, which are small
childbirth and to constrict uterine blood vessels following childbirth. spheres with walls composed of simple cuboidal epithelium (figure 10.15c,d). The
epithelial cells of the follicles synthesize the thyroid hormones, T3 and T4, which
Thyroid Gland
are stored within the follicles. Each thyroid follicle is filled with the protein
The thyroid (THIGH-royd; shield-shaped) gland synthesizes and secretes three thyroglobulin (thigh-roh-GLOB-you-lin), to which thyroid hormones are attached.
hormones: (1) triiodothyronine (T3), (2) thyroxine (tetraiodothyronine; T4), and Thyroid hormones attach to nuclear receptors in their target cells and regulate the
(3) calcitonin. It is made up of two lobes connected by a narrow band called the metabolic rate of the body (table 10.2). Between the follicles is a network of loose
isthmus (IS-muhs; a constriction). The lobes are located on each side of the connective tissue that contains capillaries and scattered parafollicular cells, or
trachea, just inferior to the larynx (figure 10.15a,b). The thyroid gland is one of the C cells, which secrete the hormone calcitonin.
largest endocrine glands. It appears more red than the surrounding tissues The thyroid gland requires iodine to synthesize thyroid hormones. Thyroxine
because it is highly vascular. It is surrounded by a connective tissue capsule. (thigh-ROK-seen) or tetraiodothyronine (TET-rah-eye-oh-doh-THIGH-roh-neen).
contains four iodine atoms and is abbreviated T4. Triiodothyronine (trie-EYE-
Page 315 oh-doh-THIE-roh-neen), contains three iodine atoms and is abbreviated T3.
Without iodine, thyroid hormones are neither produced nor secreted. A deficiency
of iodine is not as common in the United States as it once was. Table salt with
iodine added to it (iodized salt) is available in grocery stores, and vegetables grown
in soil rich in iodine can be shipped to most places.
Thyroid hormone secretion is regulated by hormones from both the
hypothalamus and pituitary. Figure 10.16 details the steps in the regulation of
thyroid hormone secretion.

Page 316

Page 317

Page 318

Figure 10.15 Thy roid and Parat hy roid Glands

(a) A nter ior v iew of th e th y r oid gland. (b) Th e fou r sm all par ath y r oid glands ar e em bedded in th e poster ior
su r face of th e th y r oid gland. (c) Th r ee-dim ensional inter pr etiv e dr aw ing of th y r oid follicles and par afollicu lar
cells. (d) Ligh t m icr ogr aph of th y r oid and par ath y r oid tissu e.
(d) ©V ictor Er osch enko
 additional TSH-releasing hormone and TSH to be secreted. Because of the
negative-feedback effect, the thyroid hormones fluctuate within a narrow
concentration range in the blood. However, a loss of negative feedback will result
in excess TSH. This causes the thyroid gland to enlarge, a condition called a
goiter (GOY-ter). One type of goiter develops if iodine in the diet is too low. As
less thyroid hormone is synthesized and secreted, TSH-releasing hormone and
TSH secretion increase above normal levels and cause dramatic enlargement of
the thyroid gland.
Because thyroid hormones are critical regulators of growth and development,
failure to maintain appropriate levels of thyroid hormones dramatically affects the
body’s functions. A lack of thyroid hormones is called hypothyroidism (high-
poh-THIGH-royd-ism). In infants, hypothyroidism can result in cretinism
(KREH-tin-ism). Cretinism is characterized by developmental delay, short stature,
and abnormally formed skeletal structures. In adults, the lack of thyroid
hormones results in a decreased metabolic rate, which can result in low body
temperature, weight gain, reduced appetite, and lethargy, among other symptoms.
An elevated rate of thyroid hormone secretion is hyperthyroidism (high-per-
THIGH-royd-ism). Hyperthyroidism causes an increased metabolic rate, extreme
nervousness, and chronic fatigue. Graves disease is an autoimmune disease that
causes hyperthyroidism. This disease occurs when the immune system produces
Figure 10.16 Regulat ion of Thy roid Hormone (T 3 and T 4) Secret ion
Th y r oid h or m ones ar e r egu lated by th e h y poth alam u s and anter ior pitu itar y .
abnormal proteins that are similar in structure and function to TSH, which
overstimulates the thyroid gland. Graves disease is often accompanied by bulging
❶ The hypothalamus secretes TSH-releasing hormone, also known as TRH. Stress of the eyes, a condition called exophthalmia (ek-sof-THAL-me-ah) (see Systems
and hypothermia cause TRH to be released from neurons within the Pathology, “Graves Disease”).
hypothalamus. It passes through the hypothalamohypophysial portal system
to the anterior pituitary.
Apply It 3
❷ TRH travels to the anterior pituitary to stimulate the secretion of thyroid-
In people with Graves disease (hyperthyroidism), the immune
stimulating hormone (TSH). system produces a large amount of a protein that is so much like
TSH that it binds to cells of the thyroid gland and acts like TSH.
❸ TSH causes increased synthesis and release of T3 and T4 into the general Unlike TSH, however, the secretion of this protein does not respond
circulation. Small fluctuations in blood TSH levels occur on a daily basis, with to negative feedback. Explain the effect of this abnormal protein on
the structure and function of the thyroid gland and the release of
a small increase at night. Increasing blood levels of TSH increase the synthesis hormones from the hypothalamus and anterior pituitary gland.
and release of thyroid hormones from thyroglobulin. Decreasing blood levels
of TSH decrease the synthesis and release of thyroid hormones. In addition to secreting thyroid hormones, the parafollicular cells of the thyroid
❹ T3 and T4 act on target tissues to produce a response. gland secrete a hormone called calcitonin (see figure 10.15c). Calcitonin is
secreted if the blood concentration of Ca2 + becomes too high. Calcitonin lowers
❺ T3 and T4 also have an inhibitory effect on the secretion of TRH from the blood Ca2 + levels to return to their normal range (figure 10.17). Calcitonin binds to
hypothalamus and TSH from the anterior pituitary. membrane-bound receptors of osteoclasts and inhibits them. Inhibition of
The negative-feedback effect of thyroid hormones on the hypothalamus and osteoclasts reduces the rate of Ca2 + reabsorption (breakdown) from bone.
pituitary results in increasing levels of thyroid hormones inhibiting the secretion Calcitonin may prevent blood Ca2 + levels from becoming overly elevated following
of TSH-releasing hormone from the hypothalamus and inhibiting TSH secretion a meal that contains a high concentration of Ca2 + .
from the anterior pituitary gland. Decreasing thyroid hormone levels allow
 Parathyroid Glands

Four tiny parathyroid (pair-ah-THIGH-royd) glands are embedded in the

posterior wall of the thyroid gland (see figure 10.15b, d). The parathyroid glands
secrete a hormone called parathyroid hormone (PTH), which is essential for
the regulation of blood calcium levels (table 10.2). In fact, PTH is more important
than calcitonin in regulating blood Ca2 + levels. PTH has many effects:

1. PTH increases active vitamin D formation through effects on membrane-bound

receptors of renal tubule cells in the kidneys. Vitamin D stimulates increased Ca2+
absorption by intestinal epithelial cells.
2. PTH secretion increases blood Ca2+ levels. PTH binds to receptors on osteoblasts. In
turn, osteoblasts secrete substances that stimulate osteoclasts to reabsorb bone.
3. PTH decreases loss of Ca2+ in the urine.
Vitamin D is produced from precursors in the skin that are modified by the liver
and kidneys. Ultraviolet light acting on the skin is required for the first stage of
vitamin D synthesis, and the final stage of synthesis in the kidney is stimulated by
PTH. Vitamin D can also be supplied in the diet.

Apply It 4
Explain why a person who stays indoors all day and lacks vitamin D
has bones that are softer than normal.

Decreasing blood Ca2 + levels stimulate an increase in PTH secretion (figure

10.17). For example, if too little Ca2 + is consumed in the diet or if a person suffers
from a prolonged lack of vitamin D, blood Ca2 + levels decrease, and PTH secretion
increases. The increased PTH increases the rate of bone reabsorption. Blood Ca2 +
levels can be maintained within a normal range, but prolonged reabsorption of
bone results in reduced bone density, as manifested by soft, flexible bones that are
easily deformed in young people and porous, fragile bones in older people.

Page 319
Homeostasis Figure 10.17 Regulat ion of Calcium Ion Blood Lev els
2+ 2+
(1 ) Blood Ca is w ith in its nor m al r ange. (2 ) Blood Ca lev el incr eases ou tside th e nor m al r ange. (3 ) Th e
Increasing blood Ca2 + levels cause a decrease in PTH secretion (figure 10.17).
par afollicu lar cells and th e par ath y r oid gland cells detect elev ated blood Ca 2+. Th e par afollicu lar cells secr ete
calcitonin; th e par ath y r oid gland cells decr ease PTH secr etion. (4 ) Th er e is less bone r eabsor ption and less u ptake The decreased PTH secretion leads to reduced blood Ca2 + levels. In addition,
of Ca 2+ fr om both th e kidney and th e intestine. (5) Blood Ca 2+ lev el dr ops back to its nor m al r ange. (6 ) Hom eostasis increasing blood Ca2 + levels stimulate calcitonin secretion, which also causes
is r estor ed. Obser v e th e r esponse to a dr op in blood Ca 2+ by follow ing th e red arrow s.
blood Ca2 + levels to decline.
Calcitonin helps prevent elevated blood Ca2 + levels, but a lack of calcitonin An abnormally high rate of PTH secretion is called hyperparathyroidism.
secretion does not result in a prolonged increase in those levels. Other One cause is a tumor in a parathyroid gland. The elevated blood levels of PTH
mechanisms controlling blood Ca2 + levels compensate for the lack of calcitonin increase bone reabsorption, which elevates blood Ca2 + levels. As a result, bones
secretion. can become soft, deformed, and easily fractured. In addition, the elevated blood
Ca2 + levels make nerve and muscle cells less excitable, resulting in fatigue and
muscle weakness. The excess Ca2 + can be deposited in soft tissues of the body,
causing inflammation. In addition, kidney stones can result.
An abnormally low rate of PTH secretion is called hypoparathyroidism.
Hypoparathyroidism can result from injury to or the surgical removal of the
thyroid and parathyroid glands. The low blood levels of PTH lead to reductions in
the rate of bone reabsorption and the formation of vitamin D. As a result, blood
Ca2 + levels decrease. In response to low blood Ca2 + levels, nerves and muscles
become excitable and produce spontaneous action potentials that cause frequent
muscle cramps or tetanus. Severe tetanus can affect the respiratory muscles;
breathing stops, resulting in death.

Adrenal Glands

The adrenal (ah-DREE-nal; near or on the kidneys) glands are two small glands
located superior to each kidney (figure 10.18a; table 10.2). Each adrenal gland has
an inner part, called the adrenal medulla (marrow, or middle), and an outer
part, called the adrenal cortex (bark, or outer). The adrenal medulla and the
adrenal cortex function as separate endocrine glands.

Figure 10.18 Anat omy and Hist ology of t he Adrenal Gland

(a) A n adr enal gland lies at th e su per ior pole of each kidney . (b) Th e adr enal glands h av e an ou ter cor tex and an
inner m edu lla. (c) Th e cor tex is su r r ou nded by a connectiv e tissu e capsu le.
(c) ©V ictor Er osch enko

Page 320

Adrenal Medulla
The adrenal medulla secretes two major hormones: (1) epinephrine (ep-ih-NEF-
rin; epi, upon + nephros, kidney; adrenaline (ah-DREN-ah-lin)), which accounts
for 80% of the adrenal medulla secretions and (2) norepinephrine, (NOR-ep-ih-
NEF-rin) which accounts for 20%. Figure 10.19 illustrates the mechanism by
which the adrenal medulla secretes its hormones.

PROCESS Figure
 1. Release of stored energy sources to support increased physical activity. For example,
glucose derived from breakdown of liver glycogen and fatty acids derived from the
breakdown of adipose tissue.
2. Increased blood pressure. Two effects of epinephrine cause an elevated blood pressure.
a. Increased heart rate.
b. Constriction of blood vessels in skin and internal organs.
3. Increased blood flow to skeletal muscle. The vasoconstriction in the internal organs and
skin blood vessels reduces blood flow to those tissues. The smooth muscle in skeletal
muscle blood vessels does not contract. That, in combination with decreased blood
flow elsewhere, explains the increased blood flow to the skeletal muscle.
4. Increased metabolic rate of several tissues, especially skeletal muscle, cardiac muscle,
and nervous tissue.

Responses to hormones from the adrenal medulla reinforce the effect of the
sympathetic division of the autonomic nervous system. Thus, the adrenal medulla
PROCESS Figure 10.19 Regulation of Adrenal Medullary Secretions and the sympathetic division function together to prepare the body for physical
Stimulation of the hypothalamus by stress, physical activity, or low blood glucose levels causes action activity and to produce the fight-or-flight response and many other responses to
potentials to travel through the sympathetic nervous system to the adrenal medulla. In response, the stress.
adrenal medulla releases epinephrine and smaller amounts of norepinephrine into the blood. These
hormones have several effects that prepare the body for physical activity. Page 321

Adrenal Cortex
How do epinephrine and norepinephrine from the adrenal The adrenal cortex secretes three classes of steroid hormones: (1)
medulla differ in their delivery to their targets from epinephrine and mineralocorticoids (MIN-er-al-oh-KOHR-ti-koydz), (2) glucocorticoids (gloo-koh-
norepinephrine released by neurons of the sympathetic nervous KOR-ti-koids), and (3) adrenal androgens (AN-droh-jens). The molecules of all
system? three classes of steroid hormones enter their target cells and bind to nuclear
receptor molecules. However, the hormones and the receptors of each class have
unique structural and functional characteristics.
❶ Secretion of adrenal medulla hormones can occur under various conditions that
As their name suggests, the mineralocorticoids regulate ion balance in the
activate the sympathetic nervous system. For example, stress, low blood
blood. The mineralocorticoids are the major secretory products of the zona
glucose, or excitement cause secretion of these hormones.
glomerulosa of the adrenal cortex. Aldosterone (al-DOS-ter-ohn) is produced in
❷ An increased frequency of action potentials conducted through the sympathetic the greatest amounts, although other, closely related mineralocorticoids are also
division of the autonomic nervous system stimulates the adrenal medulla to secreted. Aldosterone is secreted under low blood pressure conditions. It returns
secrete epinephrine and some norepinephrine into the circulatory system. blood pressure to its normal range through modulation of kidney function.
❸ These hormones bind to membrane-bound receptors in their target tissues, Aldosterone increases the rate of Na+ reabsorption by the kidneys, which
where they prepare the body for intense physical activity. increases blood levels of Na+ . The higher blood Na+ levels enhance water
reabsorption through osmosis. Recall from chapter 3 that osmosis is the diffusion
Epinephrine and norepinephrine are called the fight-or-flight hormones. They
of water toward higher solute areas. This reabsorption of water increases blood
prepare the body for intense physical activity. The major effects of the hormones
volume and thereby increases blood pressure. Aldosterone also stimulates K+
released from the adrenal medulla are
excretion into the urine by the kidneys, which lowers blood levels of K+ . In
addition, aldosterone increases the rate of H+ excretion into the urine. When
aldosterone is secreted in high concentrations, reduced blood K+ levels and
alkalosis (elevated pH of body fluids) may result. The specific effects of
aldosterone and the mechanisms controlling aldosterone secretion are discussed
along with cardiovascular system functions in chapter 13 and with kidney PROCESS Figure
functions in chapter 18.

Apply It 5
Explain the effects of reduced aldosterone secretion on blood levels
of Na+ and K+, as well as on blood pressure.

Glucocorticoids help to provide energy for cells by stimulating the increased use
of lipids and proteins. It is the middle layer of the adrenal cortex that secretes the
glucocorticoid hormones, primarily cortisol (KOR-tih-sol). The responses
are classified as metabolic, developmental, or anti-inflammatory. Glucocorticoids
cause lipid breakdown, reduce glucose and amino acid uptake in skeletal muscle,
stimulate synthesis of new glucose from precursor molecules, such as amino acid,
and increase protein degradation. Glucocorticoids also increase blood glucose
levels and glycogen deposits in cells. The glucose and glycogen are a reservoir of
molecules that can be metabolized rapidly.
Glucocorticoids decrease the intensity of the inflammatory and immune
responses by decreasing both the number of white blood cells and the secretion of
inflammatory chemicals from tissues. Synthetic glucocorticoids are often used to
suppress the immune response in people suffering from autoimmune conditions
and in transplant recipients (see chapter 14). The anti-inflammatory effect of PROCESS Figure 10.20 Regulation of Cortisol Secretion from the
cortisol is important under conditions of stress, when the rate of glucocorticoid Adrenal Cortex
secretion is relatively high. Although the ability to respond to stress is adaptive for Cortisol secretion is stimulated by the anterior pituitary hormone, ACTH.
short periods of time, responses triggered by stressful conditions are harmful if
they occur for long periods. Prolonged stress can lead to hypertension (elevated
blood pressure), heart disease, ulcers, inhibited immune system function, changes Explain why the drug cortisone (KOR-tih-sohn),
a steroid closely related to cortisol, is prescribed to treat joint
in mood, and other conditions. Humans are frequently exposed to prolonged injuries, allergies, or asthma.
psychological stress from high-pressure jobs, the inability to meet monetary
obligations, or social expectations. Although responses to stress prepare a person
❶ Corticotropin-releasing hormone (CRH) is released from hypothalamic neurons
for physical activity, increased physical activity is often not an appropriate
in response to stress or low blood glucose, and passes, by way of the
response to the situation causing the stress. Long-term exposure to stress under
hypothalamohypophysial portal system, to the anterior pituitary.
conditions in which physical activity and emotions must be constrained may be
harmful. Techniques that effectively reduce responses to stressful conditions, ❷ In the anterior pituitary, CRH binds to and stimulates cells that secrete
such as biofeedback, meditation, or other relaxation exercises, can be helpful to adrenocorticotropic hormone (ACTH).
people who are exposed to chronic stress. ❸ The middle layer of the adrenal cortex is very sensitive to ACTH. Once ACTH
The regulation of cortisol secretion is outlined in figure 10.20. binds to its membrane-bound receptors, the adrenal cortex increases cortisol
secretion.
Page 322
❹ Cortisol acts on target tissues, resulting in increased breakdown of lipids and
proteins, higher glucose levels, and increased anti-inflammatory effects.
❺ Both ACTH and cortisol act via negative feedback to inhibit CRH secretion from
the hypothalamus.
High concentrations of cortisol in the blood inhibit ACTH secretion from the
anterior pituitary, and low concentrations stimulate it. This negative-feedback
loop is important in maintaining blood cortisol levels within a controlled range of
concentration. Stress and hypoglycemia (low levels of glucose in the blood) trigger
a large increase in CRH release from the hypothalamus by causing a rapid
increase in blood levels of cortisol. In addition, CRH levels vary significantly
throughout the day.

Apply It 6
Cortisone is sometimes given to people who have severe allergies
or extensive inflammation or to people who suffer from autoimmune
diseases. Taking this substance for long periods of time can
damage the adrenal cortex. Explain how this damage can occur.

The third class of hormones, secreted by the inner layer of the adrenal cortex, is
Figure 10.21 St ruct ure of t he Pancreas
composed of the adrenal androgens, which stimulate the development of male Th e endocr ine por tion of th e pancr eas is m ade u p of scatter ed pancr eatic islets. A lph a cells secr ete glu cagon, beta
secondary sex characteristics. Small amounts of androgens are secreted from the cells secr ete insu lin, and delta cells secr ete som atostatin. Th e exocr ine por tion of th e pancr eas su r r ou nds th e
pancr eatic islets and pr odu ces digestiv e enzy m es th at ar e car r ied th r ou gh a sy stem of du cts to th e sm all
adrenal cortex in both males and females. In adult males, most androgens are intestine. Th e stain u sed for th e ligh t m icr ogr aph does not distingu ish betw een alph a, beta, and delta cells.
secreted by the testes. In adult females, the adrenal androgens influence the ©Bioph oto A ssociates/Science Sou r ce
female sex drive. If the secretion of reproductive hormones from the adrenal
cortex is abnormally high, exaggerated male characteristics develop in both males TABLE 10.3 Effects of Insulin and Glucagon on Target Tissues
and females. This condition is most apparent in females and in males before
Target Tissue Insulin Responses Glucagon Responses
puberty, when the effects are not masked by the secretion of androgens by the
testes. Skeletal muscle, Increases glucose Has little effect
cardiac muscle, uptake and
Pancreas, Insulin, and Diabetes cartilage, bone glycogen
fibroblasts, synthesis;
blood cells, increases
The endocrine part of the pancreas (PAN-kree-as) consists of pancreatic islets mammary uptake of
(islets of Langerhans), which are dispersed throughout the exocrine portion of the glands amino acids
pancreas (figure 10.21). The islets consist of three cell types, each of which Liver Increases Causes rapid increase in the breakdown of glycogen
secretes a separate hormone. (1) Alpha cells secrete glucagon, (2) beta cells glycogen to glucose and release of glucose into the blood;
secrete insulin, and (3) delta cells secrete somatostatin. These three hormones synthesis; increases the formation of glucose from amino
increases use acids and, to some degree, from lipids; increases
regulate the blood levels of nutrients, especially glucose (table 10.3). of glucose for metabolism of fatty acids
energy
Page 323 Adipose cells Increases glucose High concentrations cause breakdown of lipids;
uptake, probably unimportant under most conditions
glycogen
synthesis, lipid
synthesis
 Target Tissue Insulin Responses Glucagon Responses

Nervous system Has little effect Has no effect

except to
increase
glucose
uptake in the
satiety center

It is very important to maintain blood glucose levels within a normal range

(figure 10.22). A below-normal blood glucose level causes the nervous system to
malfunction because glucose is the nervous system’s main source of energy.
When blood glucose decreases, other tissues rapidly break down lipids and
proteins to provide an alternative energy source. As lipids are broken down, the
liver converts some of the fatty acids to acidic ketones (KEE-tonez), which are
released into the blood. When blood glucose levels are very low, the breakdown of
lipids can cause the release of enough fatty acids and ketones to reduce the pH of
the body fluids below normal, a condition called acidosis (as-ih-DOH-sis). The
amino acids of proteins are broken down and used by the liver to synthesize
glucose.

Page 324

Homeostasis Figure 10.22 Regulat ion of Blood Glucose Lev els

(1 ) Blood glu cose is w ith in its nor m al r ange. (2 ) Blood glu cose lev el incr eases ou tside th e nor m al r ange. (3 ) Th e
pancr eatic islets secr ete insu lin in dir ect r esponse to elev ated blood glu cose. (4 ) Most tissu es take u p glu cose w h en
insu lin binds to its r eceptor on th e tissu es. (5) Blood glu cose lev el dr ops back to its nor m al r ange. (6 ) Hom eostasis
is r estor ed. Obser v e th e r esponse to a dr op in blood glu cose by follow ing th e red arrow s.
 Elevated blood glucose levels stimulate beta cells to secrete insulin (IN-syu- Glucagon (GLUE-kah-gon) is released from the alpha cells when blood
lin). Additionally, increased parasympathetic stimulation associated with glucose levels are low. Glucagon binds to membrane-bound receptors primarily in
digestion of a meal stimulates insulin secretion. Increased blood levels of certain the liver, causing the glycogen stored in the liver to be converted to glucose. The
amino acids also stimulate insulin secretion. There are two signals that inhibit glucose is then released into the blood to increase blood glucose levels. After a
insulin secretion: (1) low blood glucose levels and (2) stimulation of the meal, when blood glucose levels are elevated, glucagon secretion is reduced.
sympathetic nervous system. The decrease in insulin levels allows blood glucose Somatostatin (SOH-mah-TOH-stat-in) is released by the delta cells in
to be conserved to provide the brain with adequate glucose and to allow other response to food intake. Somatostatin inhibits the secretion of insulin and
tissues to metabolize fatty acids and glycogen stored in the cells. glucagon and inhibits gastric tract activity.
The major target tissues for insulin are the liver, adipose tissue, muscles, and
the area of the hypothalamus that controls appetite, called the satiety (sa-TIE-eh-
tee; fulfillment of hunger) center. Insulin binds to membrane-bound receptors
and, either directly or indirectly, increases the rate of glucose and amino acid Apply It 7
uptake in these tissues. Glucose is converted to glycogen or lipids, and the amino How are the rates of insulin and glucagon secretion affected
immediately following a large meal rich in carbohydrates? How are
acids are used to synthesize protein. The effects of insulin on target tissues are they affected after 12 hours without eating?
summarized in table 10.3.
Diabetes mellitus (die-ah-BEE-teez MEL-ih-tus; much urine + honey or Insulin and glucagon together regulate blood glucose levels (see figure 10.22).
sweetened) is the body’s inability to regulate blood glucose levels within the When blood glucose levels increase, insulin secretion increases, and glucagon
normal range. There are two types of diabetes mellitus, type 1 and type 2. Type 1 secretion decreases. When blood glucose levels decrease, the rate of insulin
diabetes mellitus occurs when too little insulin is secreted from the pancreas. secretion declines, and the rate of glucagon secretion increases. Other hormones,
Type 2 diabetes mellitus is caused by either too few insulin receptors on target such as epinephrine, cortisol, and growth hormone, also maintain blood levels of
cells or defective receptors on target cells. The defective receptors do not respond nutrients. When blood glucose levels decrease, these hormones are secreted at a
normally to insulin. greater rate. Epinephrine and cortisol cause the breakdown of protein and lipids
In type 1 diabetes mellitus, tissues cannot take up glucose effectively, causing and the synthesis of glucose to help increase blood levels of nutrients. Growth
blood glucose levels to become very high, a condition called hyperglycemia hormone slows protein breakdown and favors lipid breakdown.
(HIGH-per-glye-SEE-mee-ah; hyper, above + glycemia, blood glucose). Because
glucose cannot enter the cells of the satiety center in the brain without insulin, Testes and Ovaries
the satiety center responds as if there were very little blood glucose, resulting in
The testes of the male and the ovaries of the female secrete reproductive
an exaggerated appetite. The excess glucose in the blood is excreted in the urine,
hormones, in addition to producing sperm cells or oocytes, respectively. The
making the urine volume much greater than normal. Because of excessive urine
hormones produced by these organs play important roles in the development of
production, the person has a tendency to become dehydrated and thirsty. Even
sexual characteristics. Structural and functional differences between males and
though blood glucose levels are high, lipids and proteins are broken down to
females, as well as the ability to reproduce, depend on the reproductive hormones
provide an energy source for metabolism, resulting in the wasting away of body
(see table 10.2).
tissues, acidosis, and ketosis. People with this condition also exhibit a lack of
The main reproductive hormone in the male is testosterone (tes-TOSS-ter-
energy. Insulin must be injected regularly to adequately control blood glucose
ohn), which is secreted by the testes. It regulates the production of sperm cells by
levels. When too much insulin is present, as occurs when a diabetic is injected
the testes and the development and maintenance of male reproductive organs and
with too much insulin or has not eaten after an insulin injection, blood glucose
secondary sexual characteristics.
levels become very low. The brain, which depends primarily on glucose for an
In the female, two main classes of reproductive hormones, secreted by the
energy source, malfunctions. This condition, called insulin shock, can cause
ovaries, affect sexual characteristics: (1) estrogen (ES-troh-jen) and (2)
disorientation and convulsions and may result in loss of consciousness.
progesterone (proh-JESS-ter-ohn). These hormones, along with the anterior
Fortunately genetic engineering has allowed synthetic insulin to become widely
pituitary hormones, FSH and LH, control the female reproductive cycle, prepare
available to diabetics.
the mammary glands for lactation, and maintain pregnancy. Estrogen and
Page 325
progesterone are also responsible for the development of the female reproductive
10.7 OTHER HORMONES
organs and female secondary sexual characteristics.
LH and FSH stimulate the secretion of hormones from the ovaries and testes. Learning Outcomes After reading this section, you should be able to
Releasing hormone from the hypothalamus controls the rate of LH and FSH
secretion in males and females. LH and FSH, in turn, control the secretion of A. Describe the functions of hormones secreted by the stomach and small intestine, the functions of
prostaglandins, and the functions of erythropoietin.
hormones from the ovaries and testes. Hormones secreted by the ovaries and
testes also have a negative-feedback effect on the hypothalamus and anterior Cells in the lining of the stomach and small intestine secrete hormones that
pituitary. The control of hormones that regulate reproductive functions is stimulate the production of digestive juices from the stomach, pancreas, and liver.
discussed in greater detail in chapter 19. This secretion occurs when food is present in the digestive system, but not at
Thymus other times. Hormones secreted from the small intestine also help regulate the
rate at which food passes from the stomach into the small intestine (see chapter
The thymus lies in the upper part of the thoracic cavity (see figure 10.1 and table 16).
10.2). It is important in the function of the immune system. The thymus secretes
a hormone called thymosin (THIGH-moh-sin), which aids the development of Page 326
white blood cells called T cells. T cells help protect the body against infection by
foreign organisms. The thymus is most important early in life; if an infant is born SYSTEMS PATHOLOGY
without a thymus, the immune system does not develop normally, and the body is
less capable of fighting infections (see chapter 14).
Graves Disease (Hyperthyroidism)
Pineal Gland

The pineal (PIN-ee-al; pinecone) gland is a small, pinecone-shaped structure Background Information
located superior and posterior to the thalamus of the brain (see chapter 8). The Over several months, Grace began to notice that she was sweating excessively and looking flushed. In
addition, she often felt her heart pounding, was much more nervous than usual, and found it difficult to
pineal gland produces a hormone called melatonin (mel-ah-TONE-in). concentrate. Then Grace began to feel weak and lose weight, even though her appetite was greater than
Melatonin is thought to inhibit the reproductive hypothalamic-releasing hormone, normal. Grace was diagnosed with Graves disease, a type of hyperthyroidism. Graves disease is caused by
gonadotropin-releasing hormone. Inhibition of the hypothalamic-releasing altered regulation of hormone secretion—specifically, the elevated secretion of thyroid hormones from the
thyroid gland. In approximately 95% of Graves disease cases, the immune system produces an unusual
hormone prevents secretion of the reproductive tropic hormones, LH and FSH antibody type, which binds to receptors on the cells of the thyroid follicle and stimulates them to secrete
from the anterior pituitary (see table 10.2). Thus, melatonin inhibits the increased amounts of thyroid hormone. The secretion of the releasing hormone and thyroid-stimulating
reproductive system. Animal studies have demonstrated that the amount of hormone is inhibited by elevated thyroid hormones. However, the antibody is produced in large amounts and
is not inhibited by thyroid hormones. A very elevated rate of thyroid hormone secretion is therefore
available light controls the rate of melatonin secretion. In many animals, short maintained. In addition, the size of the thyroid gland increases, and connective tissue components are
day length causes an increase in melatonin secretion, whereas longer day length deposited behind the eyes, causing them to bulge (figure 10.23). Enlargement of the thyroid gland is called a
causes a decrease in melatonin secretion. Some people take melatonin goiter.

supplements as a sleep aid. The function of the pineal gland in humans is not
entirely clear, but tumors that destroy the pineal gland correlate with early sexual
development, and tumors that result in pineal hormone secretion correlate with
delayed development of the reproductive system. It is not known, however, if the
pineal gland controls the onset of puberty.

Apply It 8
A tumor can destroy the pineal gland’s ability to secrete melatonin.
How would that affect the reproductive system of a young person?
Figure 10.23 Effects of Hyperthyroidism
 (a) A goiter and (b) protruding eyes are symptoms of hyperthyroidism. TABLE 10.4 REPRESENTATIVE DISEASES AND DISORDERS: Endocrine System
(a) ©Mike Goldwater/Alamy; (b) ©Ralph C. Eagle, Jr./Science Source
Condition Description
Grace was treated with radioactive iodine (131I) atoms that were actively transported into thyroid cells, where Diabetes insipidus Due to a lack of ADH from the posterior pituitary; results in excessive
they destroyed a substantial portion of the thyroid gland. Data indicate that this treatment has few side effects
urination
and is effective in treating most cases of Graves disease. Other options include (1) drugs that inhibit the
synthesis and secretion of thyroid hormones and (2) surgery to remove part of the thyroid gland. Figure 10.24 Hashimoto Autoimmune disease in which thyroid hormone secretion can be
illustrates the effects Graves disease may have on the body’s organ systems. thyroiditis decreased; metabolic rate is decreased, weight gain is possible, and
Page 327 activity levels are depressed
Primary 90% of cases due to adenoma of the parathyroid gland; causes blood PTH
hyperparathyroidism levels to increase above normal; elevated blood Ca2+ levels, weakened
bones and possible muscular weakness
Addison disease Low levels of aldosterone and cortisol from the adrenal cortex; low blood
Na+ levels, low blood pressure, and excessive urination
Gestational diabetes
Develops in pregnant women due to actions of the placental hormone,
human placental lactogen (HPL); in some women, HPL overly
desensitizes the woman’s insulin receptors; causes elevated blood
glucose levels in the mother and, if left untreated, excessive fetal growth

Page 328

E
F
F
E
C
T
S
O
F
A
G
I
Figure 10.24 Interactions Among Organ Systems and Graves Disease
N
Graves disease affects many body systems, as this diagram illustrates. G
O
N
Apply It 9 T
Explain why removal of part of the thyroid gland is an effective H
treatment for Graves disease. E
E
 N Parathyroid hormone secretion increases to maintain blood calcium levels if
D dietary Ca2+ and vitamin D levels decrease, as they often do in the elderly.
O Consequently, a substantial decrease in bone matrix may occur.
In most people, the ability to regulate blood glucose does not decrease with age.
C However, there is an age-related tendency to develop type 2 diabetes mellitus for
R those who have a familial tendency, and it is correlated with age-related increases
I in body weight.
N
E Prostaglandins are widely distributed in tissues of the body, where they
S function as intercellular signals. Unlike most hormones, they are usually not
Y transported long distances in the blood but function mainly as autocrine or
S paracrine chemical signals (see table 10.1). Thus, their effects occur in the tissues
T where they are produced. Some prostaglandins cause relaxation of smooth
E muscle, such as dilation of blood vessels. Others cause contraction of smooth
M muscle, such as contraction of the uterus during the delivery of a baby. Because of
their action on the uterus, prostaglandins have been used medically to initiate
Age-related changes to the endocrine system include a gradual decrease in the abortion. Prostaglandins also play a role in inflammation. They are released by
secretion of some, but not all, endocrine glands. Some of the decreases in damaged tissues and cause blood vessel dilation, localized swelling, and pain.
secretion may be due to the fact that older people commonly engage in less Prostaglandins produced by platelets appear to be necessary for normal blood
physical activity. clotting. The ability of aspirin and related substances to reduce pain and
GH secretion decreases as people age. However, regular exercise offsets this inflammation, to help prevent the painful cramping of uterine smooth muscle,
decline. Older people who do not exercise have significantly lower GH levels than and to treat headache is a result of their inhibitory effect on prostaglandin
older people who exercise regularly. Decreasing GH levels may explain the gradual synthesis.
decrease in bone and muscle mass and the increase in adipose tissue seen in The right atrium of the heart secretes atrial natriuretic hormone (ANH, also
many elderly people. So far, administering GH to slow or prevent the called ANP) in response to elevated blood pressure. ANH inhibits Na+
consequences of aging has not been found to be effective, and unwanted side reabsorption in the kidneys. This causes more urine to be produced, reducing
effects are possible. blood volume. Lowered blood volume lowers blood pressure (see chapter 18).
A decrease in melatonin secretion may influence age-related changes in sleep The kidneys secrete the hormone erythropoietin (eh-RITH-roh-POY-ee-tin)
patterns, as well as the decreased secretion of some hormones, such as GH and in response to reduced oxygen levels in the blood. Erythropoietin acts on bone
testosterone. marrow to increase the production of red blood cells (see chapter 11).
The secretion of thyroid hormones decreases slightly with age. Age-related In pregnant women, the placenta is an important source of hormones that
damage to the thyroid gland by the immune system can occur. Approximately 10% maintain pregnancy and stimulate milk production. These hormones are estrogen,
of elderly women experience some reduction in thyroid hormone secretion; this progesterone, and human chorionic gonadotropin (GOH-nad-oh-TROH-pin),
tendency is less common in men. which is similar in structure and function to LH. chapter 20 describes the function
The kidneys of the elderly secrete less renin, reducing the ability to respond to of these hormones in more detail.
decreases in blood pressure.
Reproductive hormone secretion gradually declines in elderly men, and women
experience menopause (see chapter 19).
Secretion of thymosin from the thymus decreases with age. Fewer functional
lymphocytes are produced, and the immune system becomes less effective in SUMMARY
protecting the body against infections and cancer.
10.1 Principles of Chemical Communication
 1. The four classes of chemical messengers are autocrine, paracrine, neurotransmitter, and Although the stimulus of hormone secretion is important, inhibition is equally
endocrine. important.
2. Endocrine chemical messengers are called hormones. 1. Humoral substances can inhibit the secretion of hormones.
10.2 Functions of the Endocrine System 2. Neural stimuli can prevent hormone secretion.
3. Inhibiting hormones prevent hormone release.
The endocrine system has 10 major functions that contribute to
homeostasis. Regulation of Hormone Levels in the Blood
10.3 Hormones Two processes regulate the overall blood levels of hormones: negative feedback
and positive feedback.
Chemical Nature of Hormones
1. Negative feedback prevents further hormone secretion once a set point is achieved.
1. There are two chemical categories of hormones: lipid-soluble and water-soluble. 2. Positive feedback is a self-promoting system whereby the stimulation of hormone
2. Lipid-soluble hormones include steroids, thyroid hormones, and some fatty acid secretion increases over time.
derivatives.
10.5 Hormone Receptors and Mechanisms of Action
3. Water-soluble hormones include proteins, peptides, and amino acid derivatives.
Water-soluble hormones circulate freely in the blood. Classes of Receptors
Proteases degrade protein and peptide hormones in the blood; the breakdown products Each of the two groups of hormones has its own class of receptors.
are then excreted in the urine. However, some water-soluble hormones have chemical
modifications, such as the addition of a carbohydrate group, which prolongs their life 1. Lipid-soluble hormones bind to nuclear receptors located inside the nucleus of the
span. target cell. Some lipid-soluble hormones have rapid actions that are most likely
mediated via a membrane-bound receptor.
Page 329 2. Water-soluble hormones bind to membrane-bound receptors, which are integral
membrane proteins.
10.4 Control of Hormone Secretion
Action of Nuclear Receptors
Stimulation of Hormone Release
Three types of stimuli result in hormone secretion: humoral, neural, and 1. Nuclear receptors have portions that allow them to bind to the DNA in the nucleus once
hormonal. the hormone is bound.
1. Humoral stimulation is exhibited by hormones that are sensitive to circulating blood The hormone-receptor complex activates genes, which in turn activate the DNA to
produce mRNA.
levels of certain molecules, such as glucose or calcium.
The mRNA increases the synthesis of certain proteins that produce the target cell’s
2. Neural stimuli cause hormone secretion in direct response to action potentials in response.
neurons, as occurs during stress or exercise. Hormones from the hypothalamus that
cause the release of other hormones are called releasing hormones. 2. Nuclear receptors cannot respond immediately because it takes time to produce the
mRNA and the protein.
3. Hormonal stimulation of other hormone secretion is common in the endocrine system.
Hormones from the anterior pituitary that stimulate hormones from other endocrine Membrane-Bound Receptors and Signal Amplification
glands are called tropic hormones.
1. Membrane-bound receptors activate a cascade of events once the hormone binds.
Inhibition of Hormone Release
2. Some membrane-bound receptors are associated with membrane proteins called G
proteins. When a hormone binds to a membrane-bound receptor, G proteins are
 activated. The α subunit of the G protein can bind to ion channels and cause them to b. Mineralocorticoids (aldosterone) help regulate blood Na+ and K+ levels and water
open or change the rate of synthesis of intracellular mediators, such as cAMP. volume. Renin, secreted by the kidneys, helps regulate blood pressure by increasing
3. Second-messenger systems act rapidly because they act on already existing enzymes and angiotensin II and aldosterone production. These hormones cause blood vessels to
produce an amplification effect. constrict and enhance Na+ and water retention by the kidney.
c. Adrenal androgens increase female sexual drive but normally have little effect in
10.6 Endocrine Glands and Their Hormones males.
1. The endocrine system consists of ductless glands. Pancreas, Insulin, and Diabetes
2. Some glands of the endocrine system perform more than one function.
1. The pancreas secretes insulin in response to elevated levels of blood glucose and amino
Pituitary and Hypothalamus acids. Insulin increases the rate at which many tissues, including adipose tissue, the
liver, and skeletal muscles, take up glucose and amino acids.
1. The pituitary is connected to the hypothalamus in the brain by the infundibulum. It is 2. The pancreas secretes glucagon in response to reduced blood glucose and increases the
divided into anterior and posterior portions.
rate at which the liver releases glucose into the blood.
2. Secretions from the anterior pituitary are controlled by hormones that pass through the 3. The pancreas secretes somatostatin in response to food intake. Somatostatin inhibits
hypothalamic-pituitary portal system from the hypothalamus. insulin and glucagon secretion and gastric tract activity.
3. Hormones secreted from the posterior pituitary are controlled by action potentials
carried by axons that pass from the hypothalamus to the posterior pituitary. Page 330
4. The hormones released from the anterior pituitary are growth hormone (GH), thyroid-
Testes and Ovaries
stimulating hormone (TSH), adrenocorticotropic hormone (ACTH), luteinizing hormone
(LH), follicle-stimulating hormone (FSH), prolactin, and melanocyte-stimulating 1. The testes secrete testosterone, and the ovaries secrete estrogen and progesterone.
hormone (MSH). These hormones help control reproductive processes.
5. Hormones released from the posterior pituitary include antidiuretic hormone (ADH) and 2. LH and FSH from the pituitary gland control hormone secretion from the ovaries and
oxytocin. testes.
Thyroid Gland Thymus
The thyroid gland secretes thyroid hormones, which control the metabolic rate of The thymus secretes thymosin, which enhances the function of the immune
tissues, and calcitonin, which helps regulate blood Ca2 + levels. system.
Parathyroid Glands Pineal Gland
The parathyroid glands secrete parathyroid hormone, which helps regulate blood The pineal gland secretes melatonin, which may help regulate the onset of puberty
Ca2 + levels. Active vitamin D also helps regulate blood Ca2 + levels. by acting on the hypothalamus.
Adrenal Glands 10.7 Other Hormones
1. The adrenal medulla secretes primarily epinephrine and some norepinephrine. These 1. Hormones secreted by cells in the stomach and intestine help regulate stomach,
hormones help prepare the body for physical activity. pancreatic, and liver secretions.
2. The adrenal cortex secretes three classes of hormones. 2. The prostaglandins are hormones that have a local effect, produce numerous effects on
a. Glucocorticoids (cortisol) reduce inflammation and break down proteins and lipids, the body, and play a role in inflammation
making them available as energy sources to other tissues. 3. ANH from the right atrium of the heart lowers blood pressure.
4. Erythropoietin from the kidney stimulates red blood cell production.
 5. The placenta secretes human chorionic gonadotropin, estrogen, and progesterone, which 17. Explain how calcitonin, parathyroid hormone, and vitamin D are involved in
are essential to the maintenance of pregnancy. maintaining blood Ca2+ levels. What happens when too little or too much parathyroid
hormone is secreted?
18. List the hormones secreted from the adrenal gland, give their functions, and compare the
means by which the secretion rate of each is controlled.
REMEMBERI 19. What are the major functions of insulin and glucagon? How is their secretion regulated?
What is the effect if too little insulin is secreted or the target tissues are not responsive
NG AND to insulin?
UNDERSTAN 20. List the effects of testosterone, estrogen, and progesterone.
DING 21. What hormones are produced by the thymus and by the pineal gland? Name the effects of
these hormones.
1. What are the major functional differences between the endocrine system and the nervous 22. List the effects of prostaglandins. How is aspirin able to reduce the severity of the
system? inflammatory response?
2. List the functions of the endocrine system. 23. List the hormones secreted by the placenta.
3. List the major differences between intracellular and intercellular chemical signals. 24. List the major age-related changes that affect the endocrine system.
4. List the intercellular chemical signals that are classified on the basis of the cells from
which they are secreted and their target cells.
5. Explain the relationship between a hormone and its receptor.
6. Describe the mechanisms by which membrane-bound receptors produce responses in CRITICAL
their target tissues. THINKING
7. Describe the mechanisms by which intracellular receptors produce responses in their
target tissues. 1. A hormone is known to bind to a membrane-bound receptor. If a drug that inhibits
8. Compare the means by which hormones that can and cannot cross the cell membrane breakdown of cAMP is given, the response to the hormone is increased. If this is
produce a response. followed by giving a second drug that prevents GTP binding, the increased response to
9. Define endocrine gland and hormone. the hormone is reversed. Based on these observations, describe the mechanism by
which the membrane-bound receptor is most likely to produce a response to the
10. What makes one tissue a target tissue for a hormone and another not a target tissue? hormone.
11. Into what chemical categories can hormones be classified? 2. Aldosterone and antidiuretic hormone play important roles in regulating blood volume
12. Name three ways that hormone secretion is regulated. and concentration of blood. The response to one of these hormones is evident within
13. Describe how secretions of the anterior and posterior pituitary hormones are controlled. minutes, and the response to the other requires several hours. Explain the difference in
response time for these two hormones.
14. What are the functions of growth hormone? What happens when too little or too much
growth hormone is secreted? 3. Jordan figured that if a small amount of a vitamin was good, a lot should be better, so he
began to take supplements that included a large amount of vitamin D. Explain the effect
15. Describe the effect of gonadotropins on the ovary and testis. of vitamin D on his blood Ca2+ levels and on the secretion of hormones that regulate
16. What are the functions of the thyroid hormones, and how is their secretion controlled? blood Ca2+ levels.
What happens when too large or too small an amount of the thyroid hormones is 4. If a person’s adrenal cortex degenerated and no longer secreted hormones, what would
secreted?
be the consequences?
5. Predict the effect of elevated aldosterone secretion from the adrenal cortex.
 6. Explain how the blood levels of glucocorticoids, epinephrine, insulin, and glucagon
change after a person has gone without food for 24 hours.
7. Stella wanted to go to medical school to become a physician. While attending college,
she knew her grades had to be excellent. Stella worked very hard and worried
constantly. By the end of each school year, she had a cold and suffered from stomach
pains. Explain why she might be susceptible to these symptoms.

Answers to this chapter’s odd-numbered critical thinking questions appear in

Appendix D

Design Elements: (Microbes in Your Body): Janice Haney Carr/CDC; (Clinical

Impact): Comstock/Alamy Stock Photo