Cellular Defense Mechanisms in the Udder and Lactation of Goats1

M. J. Paape*,2 and A. V. Capuco†

*Immunology and Disease Resistance Laboratory and †Gene Evaluation and Mapping Laboratory,
USDA-ARS, Beltsville, MD 20705

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ABSTRACT: Migration of neutrophils into mam- influenced by the presence of nucleated cytoplasmic
mary tissue provides the first immunological line of particles, stage of lactation, parity, and caprine
defense against bacteria that penetrate the physical arthritis-encephalitis. Investigations indicate that a
barrier of the teat canal. Evasion of neutrophil dry period is necessary for optimal milk production in
defenses provides an opportunity for invading bacteria dairy cows but may not be necessary in goats.
to become established. Depletion of neutrophils results However, in many other respects regulation of bovine
in a dramatic increase in susceptibility to intramam-
and caprine lactation seems to be quite similar.
mary infection. Numerous cytoplasmic particles are
Studies have demonstrated additive galactopoietic
shed from the apical surface of mammary secretory
cells during milk secretion in goats. Only those effects of growth hormone and frequent milking in
counting methods that are specific for deox- both species and a recently isolated chemical feedback
yribonucleic acid can distinguish cell-like particles inhibitor of lactation seems effective across both
from somatic cells and thereby give reliable estimates species. Increasing lactational performance has the
of somatic cell numbers in goat milk. Unlike in milk potential for decreasing milk somatic cell counts in
from dairy cows, the somatic cell count in goat milk is late lactation.

Key Words: Goats, Mastitis, Milk Somatic Cells, Lactation, Somatotropin, Milking Interval

J. Anim. Sci. 1997. 75:556–565

Introduction it is recognized that increased cell counts in cow milk

result in decreased milk yield, there is no evidence to
The first line of defense against mammary infection indicate that this situation exists in goat milk
is the teat canal. Bacteria that pass this barrier and production. Several factors contribute to this elevated
enter the teat cistern meet the second line of defense: cell count. Milk secretion in the goat is apocrine,
phagocytic leukocytes. Phagocytes, consisting of neu- compared to merocrine in cows, and results in the
trophils and macrophages, ingest and kill mastitis shedding of cytoplasmic particles into milk. Cytoplas-
pathogens. Neutrophils exhibit directed migration mic particles in the size range of milk somatic cells
toward chemical messengers produced by invading commonly found in goat milk can be mistakenly
organisms, resulting in accumulation of neutrophils in counted as somatic cells. Further, neutrophils make
the milk. This review will explore mechanisms up 50 to 70% of the somatic cell count in milk from
regulating migration of neutrophils into mammary goats free of intramammary infection, whereas neu-
tissue, factors controlling survival and function of trophils only make up 5 to 20% of the total cell count
neutrophils after they leave the circulation, and the in bovine milk. Unlike in milk from cows, cell counts
importance of this process for maximizing milk in goat milk increase with stage of lactation and
production. parity.
Somatic cell counts in milk from goats are higher In addition to the importance of leukocyte function
than somatic cell counts in milk from cows. Although to udder health and milk production, this review will
consider factors that influence milk production during
the lactation cycle of goats. The relative importance of
1Presented at the goat symposium session titled “Advances in a dry period for cows and goats will be compared and a
Physiology and Chevon Technology Research” at the ASAS 87th combination of galactopoietic treatments (e.g., growth
Annu. Mtg., Orlando, FL. hormone administration, increased milking frequency,
2To whom correspondence should be addressed: Bldg. 173,
or manipulation of the activity of feedback inhibitor[s]
BARC-East.
Received January 22, 1996. of lactation) to increase production efficiency and
Accepted August 9, 1996. persistency will be discussed.

556
 CELLULAR DEFENSE AND LACTATION 557
Neutrophil Defense of the Mammary Gland of superoxide ( O 2−) and nitric oxide (NO). Pathologi-
cal conditions such as activation of inflammatory cells
Migration (diapedesis) of neutrophils into mam- induces tissues and phagocytic cells to produce su-
mary tissue provides the first immunological line of peroxide and nitric oxide, leading to the formation of
defense against bacteria that penetrate the physical peroxynitrite (Ischiropoulos et al., 1992).
barrier of the teat canal. After an inflammatory Ingestion of pathogens by neutrophils is mediated
response is initiated, neutrophils are the first cells to by antibodies (immunoglobulins) and complement
be recruited to sites of infection. Evasion of neutrophil that bind to bacteria in a process called opsonization.
defenses provides an opportunity for invading bacteria Neutrophil receptors for immunoglobulins and comple-
to become established. Depletion of neutrophils results ment act as bridges between the neutrophil and

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in a dramatic increase in susceptibility to intramam- pathogen. Neutrophils bind immunoglobulins and
mary infection (Schalm et al., 1976). complement in the circulation. Some bound ligands
The nursing or milking stimulus induces directed are removed and new immunoglobulin and comple-
migration of fresh neutrophils into mammary tissue ment receptors are expressed during diapedesis
(reviewed by Paape et al., 1992). Thus, the normal (Berning et al., 1991; DiCarlo and Paape, 1992;
sterile mammary gland is supplied with a constant Worku et al., 1994a; Paape et al., 1996). Also,
source of neutrophils. However, once in the lumen of interferon-gamma, a T-cell-derived cytokine secreted
alveoli, ingestion of fat and casein causes a loss in in response to inflammation, induces a 4.5-fold in-
phagocytic and bactericidal functions and leads to crease in IgG2 receptors (Worku et al., 1994b). Thus,
death of neutrophils (Paape and Wergin, 1977). the neutrophil now has more receptors for a more
Milking removes compromised neutrophils, which are efficient recognition of opsonized bacteria, resulting in
replaced by healthy neutrophils, thus enhancing a more rapid ingestion and elimination of invading
defense against bacterial infection. This phenomenon pathogens. During phagocytosis of pathogens, cytosolic
could partially explain the reduced incidence of granules fuse with the invaginating plasma mem-
clinical mastitis for cows milked four times a day brane to form the phagolysosome, into which they
compared to cows milked two times a day (Hillerton, release their contents, thereby creating a highly toxic
1991). microenvironment (Paape and Wergin, 1977).
In healthy animals, production and destruction of Monoclonal antibodies were developed to neutrophil
neutrophils is tightly regulated, which keeps their surface antigens that identified four subpopulations of
number in blood, milk, and tissue constant (Jain, circulating neutrophils (Guidry et al., 1992). The
1986). Neutrophils mature in the bone marrow and physiological significance of neutrophil heterogeneity
are released into the circulation, where they spend is not understood, but inflammation of the mammary
approximately 9 h before migrating into tissue (Carl- gland alters the distributions of subpopulations in the
son and Kaneko, 1975). Diapedesis of neutrophils into circulation (Jain et al., 1991). Under normal condi-
mammary tissue, where they survive for 1 to 2 d, tions, blood may contain a mixture of normal, primed,
occurs at a low level for immune surveillance. activated, and senescent neutrophils. Further, not all
Senescent neutrophils are thought to undergo apopto- of the circulating neutrophils are phagocytically,
sis (programmed cell death) before ingestion by chemotactically, and oxidatively active, and differ-
macrophages (Squier et al., 1995). The significance of ences exist among individuals in these neutrophil
this process is that this prevents unwanted disintegra- functions (Paape et al., 1978; Salgar et al., 1991;
tion in vivo, which would cause release of toxic Berning et al., 1993). This variation might partially
chemicals and cause mammary tissue damage. Neu- explain the difference in susceptibility to intramam-
trophils rapidly migrate into mammary tissue and mary infection that exists among animals within a
milk in response to inflammation. Chemotactic factors species.
released by infectious bacteria and other components Lactating dairy goats are exposed to thousands of
of the immune system are the signals for neutrophil Gram-negative bacteria and harbor many potential
recruitment to sites of infection. However, this influx pathogens on their skin and mucosal surfaces. Despite
of neutrophils is a double-edged sword. They may this high rate of exposure, intramammary infections
cause an inflammatory reaction that results in the by this class of bacteria is low compared to infections
elimination of infection but also tissue damage that by Gram-positive bacteria. On average, 1% of the
leads to fibrosis and impaired mammary function mammary glands in a dairy goat population have
(Nickerson and Heald, 1981; Capuco et al., 1986; intramammary infections with Gram-negative bac-
Akers and Thompson, 1987). Neutrophils promote teria, compared to an infection rate of 15 to 55% with
tissue injury and disturbed mammary function via 1 ) Gram-positive bacteria (Dulin et al., 1983; Poutrel
reactive oxygen metabolite generation (the respira- and Lerondelle, 1983; Contreras et al., 1995). It has
tory burst) and 2 ) granular enzyme release (degranu- been estimated that 2,000 to 4,000 milkings are
lation) (Miller et al., 1993; Kehrli and Shuster, required to observe one new intramammary infection
1994). Peroxynitrite, produced during inflammation, by a Gram-negative organism (Eberhardt, 1977). For
has recently been implicated as a major cytotoxic Gram-positive organisms this estimated frequency is 1
agent. Peroxynitrite (ONOO −) is the reaction product in 600 milkings (O’Shea, 1985).
558 PAAPE AND CAPUCO

Several human cell-surface receptors on leukocytes Table 1. Comparison of methods for estimating
(CD14, CD18, and carbohydrate) have been identified somatic cells in milk from 24 goat halvesa
as crucial in the control of infections by Gram-negative
bacteria (Anderson and Springer, 1987; Boner et al., Cell counting method Cells × 105/mL milk
1989; Maliszewski and Wright, 1991). Lipopolysac-
DMSCC-DNA specific stain 3.03b
charide ( LPS) is a complex glycolipid released by Fossomatic cell counter 3.40b
Gram-negative bacteria. Biological effects of LPS Coulter cell counter 6.44 c
include the induction of endotoxin-shock syndrome, DMSCC-nonspecific stain 7.92 c
nonspecific activation of the immune system, and Standard error 1.13
activation of the complement cascade (Van Miert, aAdapted from Dulin et al., 1982.

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b,cMeans with same letter are not significantly different ( P >
1991). The CD14 receptor is a 53-kDa phosphoinositol
.05).
( PI)-linked protein known to be present on human
monocytes and macrophages and, to a lesser degree,
on neutrophils (Jayaram and Hogg, 1989; Landmann uninfected goats are higher than milk somatic cell
et al., 1991). It binds LPS with a 60-kDa serum acute counts for uninfected cows (Dulin et al., 1983; Poutrel
phase protein, LPS-binding protein ( LBP) (Shumann and Lerondelle, 1983). On average, somatic cell
et al., 1990). Release of the cytokine tumor necrosis counts in milk from cows free from intramammary
factor ( TNF) is due to the binding of the LPS-LBP infection range from 40 to 80 × 103/mL. In milk from
complex to the CD14 molecule (Shumann et al., 1990; goats free from intramammary infection counts range
Dentener et al., 1993). Tumor necrosis factor is a
from 50 to 400 × 103/mL. A number of factors have
potent activator of leukocytes and enhances the
been reported to contribute to the high milk somatic
phagocytosis and killing of mastitis pathogens by
cell counts for goats. Milk secretion in the cow is
bovine neutrophils (Kabbur and Jain, 1995). Under
merocrine, and secretion in the goat is apocrine
defined conditions, the CD14 receptor can also medi-
(Wooding et al., 1970). As a result, cytoplasmic
ate phagocytosis of LBP-coated Gram-negative bac-
particles are shed into milk from the apical portion of
teria (Wright et al., 1989).
mammary secretory cells (Figure 1). Although the
Recent findings indicate that bovine neutrophils
majority of these particles are generally anucleated,
have the capacity to bind antihuman CD14 and CD18
some of these particles have been observed to contain
monoclonal antibodies, indicating that CD14 and
nuclear fragments (Figure 2). To what extent these
CD18 on human and bovine neutrophils share a
nucleated cytoplasmic particles contribute to the total
common antigenic determinant (Paape et al., 1996).
milk somatic cell count is presently unknown. Because
In this study, it was also shown that a large number of
of the presence of anucleate cytoplasmic particles, only
neutrophils in milk of normal mammary glands
cell counting procedures that are specific for DNA
expressed CD14 and at a higher density than did
(Fossomatic electronic cell counter, direct microscopic
blood neutrophils. Endotoxin-induced migration did
cell counts using DNA specific stains) should be used
not cause increased expression of CD14 on mammary
for estimating concentration of somatic cells in goat
neutrophils compared to blood neutrophils. Thus, it
milk (Table 1). Particle counters such as the Coulter
seems that factors present in milk of normal mam-
electronic cell counter and direct microscopic cell
mary glands upregulate expression of CD14. En-
counts using stains that are not DNA-specific should
dotoxin-induced migration also increased the percen-
tage of neutrophils expressing CD18 compared to not be used (Dulin et al., 1982).
mammary neutrophils before injection of endotoxin. Other factors contributing to the high somatic cell
Similar to results obtained with CD14, it also seems count in goat milk are stage of lactation, parity,
that factors in milk upregulated expression of CD18. intramammary infection, and caprine arthritis-en-
Ability of neutrophils to adhere to and phagocytose cephalitis virus infection (Dulin et al., 1983; Ryan et
Escherichia coli was observed in the absence of al., 1993; Zeng and Escobar, 1995). It was recently
opsonins (Paape et al., 1996). Lectin-carbohydrate determined that more than 90% of the variation in
interactions also seemed to be important in regulating milk somatic cell counts in goats was not due to
opsonic phagocytosis of E. coli by neutrophils. These intramammary bacterial infection (Wilson et al.,
recent findings indicate that mammary neutrophil cell 1995). They reported that increasing days in milk and
surface CD14, CD18, and carbohydrate receptors may month of the year were among the most important
be important in controlling infections by Gram- factors contributing to increased cell count in the
negative bacteria such as E. coli. absence of intramammary infection. To a lesser
extent, parity and reduced milk production also
contributed significantly to increased cell count. In-
Somatic Cells in Goat Milk terestingly, 75% of the variation in does free of
intramammary infection was unexplained. It was
Somatic cells are used as an index of milk quality hypothesized that this unexplained variation could be
for cow and goat milk. Milk somatic cell counts for due to infections by mycoplasmas, caprine arthritis
 CELLULAR DEFENSE AND LACTATION 559

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Figure 1. Transmission electron micrograph of lactating goat mammary gland. The alveolar lumen (L) is bounded
by epithelial cells whose apex has external microvilli (V) and internal granular accumulations (G) in the endoplasmic
reticulum that resemble those found in the “cytoplasmic particles” (CP) of milk. Some of the cytoplasmic particles
being shed from the apical surface of the secretory cells contain nuclear material (N). Bar = 10 mm.

and encephalitis virus and anaerobic bacteria. Unlike higher milk somatic cell count. Because somatic cell
in milk from goats, somatic cell counts in milk from counts in goat milk are influenced by normal physio-
cows free from intramammary infection are not logical factors that do not affect somatic cell counts in
affected by stage of lactation and parity (Paape et al., cow’s milk, regulating goat dairies based on standards
1975). Furthermore, the composition of the somatic established for cows is not appropriate.
cells in milk differs between goats and cows. For
animals free of intramammary infection, neutrophils
constitute 5 to 20% of the somatic cells in cow milk
The Lactation Cycle
and 45 to 74% in goat milk (Dulin et al., 1983; Miller
Milk production of goats and cows typically peaks 3
et al., 1991). This suggests that leukocyte migration
to 4 wk after parturition and progressively declines
into goat milk proceeds at a faster rate than migration thereafter. In contrast to other species, normal
into cow milk and may contribute to a naturally management of dairy cows and goats results in an
560 PAAPE AND CAPUCO

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Figure 2. Electron micrograph of a “cytoplasmic particle” shed into the milk by the mammary epithelium of a goat.
The particle contains nuclear material (arrow) derived from the mammary secretory cell. Bar = 2 mm.

overlap of lactation and pregnancy. Cows are gener- lactation, or to permit necessary growth and differen-
ally pregnant for 60 to 70% of their lactation, whereas tiation events within the mammary gland during this
goats, which are seasonal breeders in temperate period. Although the data are not definitive, they
climates, may be pregnant and lactating for the last strongly suggest that a dry period is necessary for
20% of the lactation cycle. Following cessation of reasons other than nutritional (Swanson, 1965; Smith
milking before parturition, the mammary gland must et al., 1966, 1967). Recently, aspects of mammary
prepare for the next lactation. Processes of mammary growth during the dry period have been investigated
growth and differentiation occur during this nonlactat- in cows at the Beltsville Agricultural Research Center
ing or “dry” period between successive lactations. Milk (Capuco et al., 1997). Multiparous Holstein cows were
production efficiency can be increased by development dried off 60 d before expected parturition or were
and use of schemes that increase persistency of milked twice daily during this prepartum period. Cows
lactation and minimize the duration of the dry period. were slaughtered at 53, 35, 20, and 7 d prepartum and
In cows, a dry period of at least 40 d seems total mammary DNA and thymidine incorporation
necessary to maximize milk production in the follow- into mammary tissue slices was determined (Figure
ing lactation (Swanson, 1965; Coppock et al., 1974; 3). There was no net loss of mammary cells (DNA)
Sorensen and Enevoldsen, 1991). This may be to during the dry period, and total number of mammary
permit restoration of body reserves before the next cells increased with advancing stages of the dry
 CELLULAR DEFENSE AND LACTATION 561

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Figure 4. Parenchymal volume of caprine udder-
halves continuously milked during the prepartum
period or dried off 24 wk before expected parturition.
Volume was determined by magnetic resonance imag-
ing. Adapted from Fowler et al., 1991.

One gland was milked during the prepartum period

and the other was dried off 24 wk (170 d ) before
parturition. In this experiment, magnetic resonance
Figure 3. Proliferation of mammary cells during the imaging was used to monitor parenchymal volume as
dry period. Cows were dried off (all quarters) 60 d an index of mammary growth and involution (Figure
before expected parturition or were milked (all quarters) 4). Mammary parenchymal volume in both udder
during the prepartum period. Panel A: Total mammary halves decreased to the same minimal volume at wk
DNA content of udder-halves from dry (solid bars) and 13. The volume then increased more rapidly in the dry
from lactating (cross-hatched bars) cows. DNA content gland than in the lactating gland, so that the dry
did not differ between dry and lactating cows. Panel B: gland had a significantly greater volume at parturi-
Incorporation of [3H]thymidine by mammary tissue tion than the continuously milked gland. Parenchymal
from dry (solid bars) and from lactating (cross-hatched volume in the milked gland continued to increase
bars) cows. Incorporation by mammary tissue from dry during early lactation when parenchymal volume in
cows was greater (P < .05) than that from lactating cows. the gland that had experienced a dry period declined.
There was no difference in milk production between
glands. Indeed, at no stage of lactation was milk yield
of glands that had experienced a dry period numeri-
period. Total DNA did not differ between mammary cally greater than that of continuously milked glands,
glands of dry and lactating cows; however, increased even though those glands were larger than continu-
DNA synthesis in dry cows indicated that replacement ously milked glands during the first few weeks after
of mammary cells increased during the dry period. parturition. These data suggest that a dry period is
Autoradiographic localization of incorporated not necessary for optimizing milk production in the
[3H]thymidine indicated that the replicating cells were next lactation in goats. Why goats and cows seem to
primarily (> 90%) epithelial. Thus, in cows the dry differ in this regard is an important question.
period may be important for replacing senescent cells However, the effect of a half-udder experimental
before the next lactation. Furthermore, although cows design should be considered. It is plausible that
seemed to enter the next lactation with the same milking one gland during the prepartum period
number of mammary cells regardless of whether they inhibited the ability of the opposite gland to produce
had a dry period, a greater percentage of those cells maximal quantities of milk during the subsequent
were epithelial in cows that had a dry period. lactation, or that milk production was increased in
In contrast to cows, a dry period does not seem glands milked continuously when the opposite gland
necessary for optimal milk production in dairy goats. was dried off. When one of an udder’s mammary
Fowler et al. (1991) investigated the necessity for a glands is no longer milked, milk production (Hender-
dry period using a within-animal, half-udder design. son and Peaker, 1983) and mammary growth (Capuco
562 PAAPE AND CAPUCO

and Akers, 1990) increase in a compensatory fashion (Knight et al., 1990), followed by proliferation of
in the lactating gland within that udder. Conversely, secretory tissue. Increased activity and proliferation of
involution is inhibited in the nonlactating gland mammary cells in response to increased milking
(Turner and Reineke, 1936; Akers and Keys, 1984). frequency also occurs in dairy cows (Hillerton et al.,
The potential interaction of glands of differing lacta- 1990).
tional state within an udder on cell turnover within When growth hormone administration and in-
the glands is unknown. Despite the uncertainties, creased milking frequency are combined, the treat-
half-udder experiments with goats suggest that, un- ments are additive but not synergistic (Knight et al.,
like in cows, a dry period is not important for maximal 1990, 1992). Data from Knight et al. (1990) are
lactation in goats. Additional study is warranted to summarized in Figure 5. Beginning during midlacta-

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examine potential species differences. tion (wk 19), goats were administered recombinant
There is little information available to indicate bovine growth hormone (.15 mg/kg BW) or vehicle.
whether changes in secretory activity during the One gland of each goat was milked twice daily and the
course of lactation are the result of changes in cell other three times daily. In addition to the additive
number or cellular activity. Anderson et al. (1981) effect of the treatments, data indicate that persistence
demonstrated that the number of mammary cells of lactation was increased in glands of growth
increases during early lactation in goats. Knight and hormone-treated goats milked three times daily
Peaker (1984) determined udder volume by water (Figure 5A). Although parenchymal growth occurred
displacement and obtained mammary biopsies at in response to increased milking frequency and growth
various times during first lactation. By extrapolating hormone administration, the growth was due to
data from biopsies to the entire gland, they demon- hypertrophy rather than hyperplasia (Figure 5B). In
strated that increases in milk production during early no case did the quantity of DNA differ from that of the
lactation are first the result of an increase in cell mammary gland sampled before treatment. Because
number followed by an increase in activity per cell. glands did not differ with regard to thymidine
During the declining phase of the lactation curve, incorporation rate, the differences in DNA content
decreased cell number was the predominant compo- among glands at wk 22 can be attributed to treatment
nent responsible for decreased milk yield. However, effects on longevity of existing epithelial cells. The
during late lactation, when the goats were pregnant, retention of cell number in the glands of growth
cell activity declined. Similar studies have not been hormone-treated goats, milked three times daily, is
performed in dairy cows. consistent with the increased persistence of milk
Development of schemes to alter the lactation curve production in this group.
would provide methods for increasing milk production Increased milking frequency is hypothesized to
efficiency and profitability. Two potential methods increase milk production by lessening the accumula-
have been investigated in recent years, growth hor- tion of a feedback inhibition of milk secretion. Because
mone administration and milking frequency. frequent milking of one udder-half has no effect on
Growth hormone has been shown to be galac- milk secretion by the other half, it is clear that milk
topoietic in cows and goats (Peel et al., 1983; Mepham removal and not systemic effects of milk plays an
et al., 1984). Several lines of evidence indicate that important role in establishing secretion rate (Linzell
exogenous growth hormone does not act directly on and Peaker, 1971). By infusing isotonic sucrose into
mammary tissue (Gertler et al., 1983; Akers, 1985; the udder of goats after milking, Henderson and
McDowell et al., 1987). Rather, its galactopoietic Peaker (1984) demonstrated that physical distension
effects are likely to be produced by effects on nutrient does not cause the observed reduction in milk
partitioning (Peel and Bauman, 1987) and through a secretion toward the end of a milking interval. They
hormone intermediary, such as the insulin-like growth concluded that accumulation and negative feedback by
factors, affecting mammary tissue (Gluckman et al., a local, chemical inhibitor is responsible. Indeed a
1987; Prosser et al., 1994). Data indicate that 7.6-kDa polypeptide that inhibits milk synthesis in
although growth hormone administration is mammo- vitro and in vivo has been isolated from whey (Wilde
genic prepubertally (Johnsson et al., 1986; Sejrsen et et al., 1988, 1995). N-terminal amino acid analysis of
al., 1986), it does not bring about an increase in the polypeptide yielded a sequence of 12 amino acids
mammary cell number during pregnancy (Lee and with no homology with other characterized milk
Forsyth, 1988) or lactation (Capuco et al., 1989; proteins (Wilde et al., 1995). The putative feedback
Knight et al., 1990; Binelli et al., 1995). During inhibitor of lactation ( FIL) is secreted by mammary
lactation, growth hormone seems to increase milk epithelial cells (Wilde et al., 1995) and rapidly and
production by virtue of effects on nutrient partitioning reversibly inhibits milk synthesis in vitro (Rennison
and cardiovascular adaptations (Knight et al., 1990; et al., 1993). When FIL is infused into the mammary
Binelli et al., 1995). gland cistern, milk yield is decreased (Wilde et al.,
Increasing milking frequency enhances milk 1988, 1995). However, maximum inhibition of milk
production of goats, due to a rapid increase in activity production is reached after 2 d and does not return to
of mammary secretory cells, often (Wilde et al., 1987; normal until the 4th day. These data suggest that if
Knight et al., 1990), but seemingly not always FIL is the endogenous feedback inhibitor of lactation,
 CELLULAR DEFENSE AND LACTATION 563
mL to the 750,000/mL standard for cow milk.
However, SCC for goats is naturally higher than SCC
for cows, and it increases with stage of lactation. Milk
secretion in the goat is apocrine, compared to mero-
crine secretion in cows, and results in the shedding of
nucleated cytoplasmic particles into milk, which are
included in SCC. Investigations of mammary prolifer-
ation, cell death, and differentiation during the dry
period and lactation may provide a means to extend
lactation and to limit the non-productive dry period.

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Furthermore, the combination of galactopoietic treat-
ments (e.g., growth hormone administration, in-
creased milking frequency, or manipulation of the
activity of feedback inhibitor[s] of lactation) offer
fertile areas for research to increase production
efficiency and persistency and potentially lower milk
somatic cell counts in late lactation.

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