INTEGRATION & COORDINATION OF

PHYSIOLOGICAL ACTIVITIES:
regulation and control of body
functions
Kwame Yeboah
• Endocrine and nervous systems coordinate
complex body functions.
• Classic distinction between these two the
medium of communication of chemical
messengers.
– Endocrine: blood-carried chemicals
– nervous system: local chemical release
(neurotransmitter).
 NEUROENDOCRINE SYSTEM
• Nerves in the posterior pituitary release
oxytocin and antidiuretic hormone, which act
on the breast and kidneys, respectively;
• Nerves release epinephrine from the adrenal
medulla, which acts on the heart, skeletal
muscle, and the liver;
• Nerves of the hypothalamus secrete
chemicals (releasing hormones) that act on
the anterior pituitary to cause hormone
release.
 ENDOCRINE PHYSIOLOGY
• Concerned with information transfer and
chemical communication among cells/tissue
• Two classes of cells involved:
– Secreting cell: produce molecular effector
– Target cell: express receptor protein where the
effector binds
Forms of communication
A B

C D

Neurocrine signals
 Classification of Hormones
• Hormones are divided into four groups based
on chemical structure:
1. amines (come from the amino acid tyrosine),
2. peptides (less than 20 amino acids),
3. small proteins (more than 20 amino acids),
4. steroids (come from cholesterol
 TABLE MAJOR HORMONES GROUPED BY CHEMICAL STRUCTURE
AMINES PEPTIDES PROTEINS STEROIDS
Dopamine Antidiuretic Adrenocorticotropic Aldosterone
hormone (ADH) Hormone (ACTH)
Epinephrine Gonadotropin- releasing Calcitonin Cortisol
hormone (GnRH)
Thyroxine Melanocyte-Stimulating Human chorionic Estradiol
(T4) hormone (MSH) gonadotropin (hCG)
Triiodothy- Oxytocin Human placental Estriol
ronine (T3) lactogen (hPL)
Thyrotropin-releasing Corticotropin-releasing
Progesterone
Hormone (TRH) hormone (CRH)
Somatostain Glucagon Testosterone
Growth hormone (GH) 1,25-vitamin D
Growth hormone-releasing
hormone (GHRH)
Follicle-stimulating hormone (FSH)
Insulin
Insulin-like growth factor (IGF-1)
Luteinizing hormone (LH)
Parathyroid hormone (PTH)
Prolactin
Thyroid-stimulating hormone (TSH)
 Hormone synthesis
1. Protein/peptide hormones
• Endoplasmic reticulum: mRNA
preprohormone
• Golgi apparatus: preprohormone
prohormone + signal peptide
– Cleavage of additional peptides
– Package into secretory granules for release
2. Steroid hormone: from cholesterol
3. Amine hormone: derivative of aa tyrosine
Regulation of hormonal secretion
• Negative feedback
– Biologic action of the hormone directly or
indirectly inhibits secretion of the hormone
– Self-limiting
– Most commonly applied principle
• Positive feedback
– Biologic action of the hormone directly or
indirectly cause more secretion of the hormone
– Explosive and self-reinforcing
– rare
• Regulation of
cortisol and
epinephrine
conc. In
plasma
Control of blood glucose
 Regulation of receptor
1. Down-regulation: decrease in the
number/sensitivity of the receptors
– Eg in uterus, progesterone down-regulates its
own receptor and that of estrogen
2. Upregulation: increase in the no. /sensitivity
of the receptors
– eg in the ovary, estrogen upregulates its
receptors and that of LH during ovulation
 Role of the liver
• The liver produces binding proteins for
hydrophobic hormones
– Eg. Cortisol-binding protein, thyroid-binding
protein, estrogen/testosterone binding protein
• For 1. transportation 2. modulation
 biorhythms
• Most hormones exhibit cyclical events
• Circadian rhythm: 24-hr cycle
– Pacemaker: suprachiasmatic nuclei in anterior
hypothalamus
– Inputs from the retina and many other brain
regions
– Can be reset by melatonin or neuropeptide Y.
• Ultradian rhythm: within circadian rhythm
– Cortisol: pulsatile release every 4-hrs
– Origin is unknown
Hypothalamus as endocrine organ
• Several connections to other brain centres
• Regulates autonomic functions
• Secretes neuropeptides that regulates higher
brain functions
• Regulates sleep-waking rhythm
• Psychogenic factors like stress
• Neurons synthesize hormones, transport it to
the axon terminal for release. Eg ADH,
Oxytocin
 Pituitary gland/hypophysis
• Lies close to the median portion of basal
hypothalamus. Connected by the pituitary
stalk
• The stalk contains both blood vessel and
neurons
• The pituitary is divided into 3 portions:
• Anterior/adenohypophysis
• Posterior/neurohypophysis
• Intermediate/pars intermedia: rudimentary in humans
 Hypothalamic control of
adenohypophysis
• Anterior pituitary linked to hypothalamus by
hypothalamic-hypophysial portal system
• Hypothalamus secretes releasing
hormone/liberins and inhibitory
hormones/statins
• General features of hypothalamic-pituitary
axis hormones
– Pulsatile release
– Superposition of circadian and ultradian rhythm
on pulsatile release
– Feedback control by both short and long loops
Cell types in anterior pituitary
 Clinical correlates
• Damage to the pituitary stalk
• All anterior pituitary hormones decreases except prolactin.
Why? PIF, chronic inhibition removed!
• Constant infusion of GnRH
• Cause decrease in FSH and LH due to downregulation of GnRH
receptors on gonadotrophs. All hormones of the
hypothalamic-pituitary axis are pulsatile except TRH
• Sheeshan syndrome: postpartum hypopituitarism
• In pregnancy, the pituitary enlarges and vulnerable to
infarction. In cases of postpartum haemorrhage, followed by
arteriolar spasm, the pituitary necrosed. Symptoms vary
depending on the extent and location of the pituitary
damage. 32% of women with severe postpartum
haemorrhage have some degree of pituitary insufficiency.
 Growth hormone
• Most important for normal growth to adult
size
• Similar structure with prolactin and human
placental lactogen
• Hypothalamic control: GHRH and somatstatin
– GHRH: increases GH synthesis and secretion
– GHIH/somatostatin: decreases GH syn. and secre.
• GH is released in pulsatile fashion
• GH secretion decrease during 6th decade and
later life.
 Regulation of GH secretion
• Secretion is increased by sleep, starvation,
stress, puberty-related hormones, exercise,
hypoglycaemia
• Secretion decreased by somatostatin,
somatomedins, obesity, hyperglycaemia and
pregnancy
• Somatomedins produced y the liver and
other cells have a longer half-life than GH
 Actions of GH
• Direct actions
– ↓cellular glucose uptake (diabetogenic)
– ↑lypolysis
– ↑protein synthesis in muscle mass and ↑lean
body mass
– ↑production of IGF
• Actions via somatomedins
– ↑protein synthesis in chondrocytes and ↑linear
growth (pubertal growth spurt)
– ↑protein synthesis in muscle mass and ↑lean
body mass
– ↑protein synthesis in most organs and ↑organ
mass
 Pathophysiology of GH
• Deficiency of GH
– Prepuberty: failure to grow, short stature, mild
obesity and delayed puberty
• Causes:
– Lack of anterior pituitary GH
– Hypothalamic dysfunction (↓GHRH) Laron dwarfism
– Failure to generate IGF
– GH receptor deficiency: congo dwarfism
– Postpuberty: more sensitive to insulin-induced
hypoglycaemia
• Very treatable, no serious complications.
• Excess GH production
– Before puberty: gigantism
– After puberty: acromegaly
• Associated with increased periosteal bone growth,
increased organ size and glucose intolerance.
• Enlargement of the hands and feet, facial overgrowth
and protrusions of the lower jaw (prognatism),
↑amount of body proteins and ↓ amount of body
fats, enlarged visceral organs and impaired cardiac
functions.
• Can be treated with somatostatin analogues eg.
octreotide
 Prolactin
• Lactogenesis and breast development (in
conjuction with estrogen)
• Hypothalamic control
– TRH: increased production
– PIH/dopamine: decrease production
• Negative feedback
– Prolactin regulates its production by stimulating
hypothalamic dopamine release.
 Actions of prolactin
• Milk production in breast (casein &
lactalbumin)
• Breast devpt (in supportive role with
estrogen)
• Inhibits ovulation by regulating GnRH
• Inhibits spermatogenesis by decreasing GnRH
 Pathophysiology
• Prolactin deficiency (destruction of ant.
Pituitary)
– Failure to lactate

• Hyperprolactinemia
– Causes
• Lesions affecting hypothalamus or pituitary stalk
• Prolactin-secreting adenomas in the anterior pituitary
• Medications such as dopamine antagonists
 Hyperprolactinemia
• In women,
– Amenorrhea
– Galactorrhea (inappropriate milk production)
– Low serum levels of estradiol
• In men,
– Galactorrhea Treatment include surgical
– Decreased libido removal of tumor or
medical treatment with
– Impotence
bromocriptine.
– Hypogonadism
– Low serum levels of testosterone.
 Posterior pituitary
• Two hormones
1. Oxytocin
2. ADH/arginine vasopressin: considered with
respect to body fluid control.
 Oxytocin
• strong stimulant for the contraction of
smooth muscle in the uterus and the distal
portion of the mammary gland duct system
– the presence of estrogen (which enhances
contraction) and progesterone (which inhibits
contraction).
– Upregulation of oxytocin in late pregnancy
– Oxytocin-induced
– uterine contractions are powerful and may be
essential for the birth process
– Can be used to promote labour and reduce
postpartum haemorrhage.
• promotes maternal behavior toward the
newborn
• Oxytocin-mediated contractions of the uterus
(in women) and the vas deferens (in men) are
also observed during orgasm
• Smooth muscle contractions in the mammary
glands result in transport of milk to the
lactiferous sinuses and subsequent milk
ejection
 Regulation of oxytocin secretion
• mechanical stimulation of the breast nipple,
such as occurs in suckling, or of the vagina
and uterus
• emotional correlates of human reactions to
sexual excitement or the crying of a baby
Questions?