Download Section 2 Lactation Physiology

‫فیزیولوژی تولید و ترشح شیر‬
Lactation Physiology
(part 2)
By: A. Riasi
(PhD in Animal Nutrition & Physiology)
 At
the end of this section students will be able to reply
 How is the blood flow of mammary gland?
 What is the importance of the udder lymphatic network?
 What is the neuroendocrine reflex of milk ejection?
 How is immunoglobulin transport in the mammary gland?
 What is galactopoeisis?
 How change the mammary gland physiology during the dry period?
 What are the allometric and isometric growth of mammary gland?
 What is the role of hormones in mammogenesis?

Mammary blood supply
 Milk synthesis rate depend to the rate of blood flow in udder.
 Blood flow in the mammary gland increase before parturition.
 The efficiency of extraction of the components from the blood
while it passes through the udder is more important.

Mammary blood supply

Mammary lymphatic network
Adapted from Khol et al., 2012

Mammary lymphatic network

Mammary lymphatic system
 The extensive lymph drainage from the udder
 In goat 6/5 – 35 ml/h
 In cows 1300 ml/h
 In general lymph drainage is about 1/6 liter per 1 kg of milk
 Lymph is a clear, colorless liquid with a composition similar to
blood plasma.

Udder edema
 Udder edema is swelling of the udder.
 It occurs to some degree in most cows at calving time.
 Fluid accumulates between skin and glandular tissue, as well as
in the gland.
 Udder edema is often caused by an imbalance of hydrostatic and
osmotic pressures.
 This may occur because of damage to the capillary walls or
obstruction of the lymphatic system.

Udder edema

Mammary nervous system
 The efferent innervation of the mammary gland is entirely
sympathetic in origin.
 Innervation of the udder is sparse compared with other tissues.
 Effect of sensory nerves found in the teats and skins in milk
ejection
 No parasympathetic innervation to the gland.
 Sympathetic nerves are associated with the arteries but not with
alveoli
 There is no innervation of the secretory system
 Few nerves go to the interior of the udder

Mammary nervous system
Adapted from F. Husvéth 2011

Milk ejection
 Role of oxytocin in milk ejection
 The time from the start of a tactile stimulation until the
occurrence of milk ejection
 A neuroendocrine reflex for milk ejection reflex
 The reflex has two pathways:
Afferent Pathway (neural)
Efferent Pathway (hormonal, blood-borne)

Milk ejection
 Other mechanisms for milk ejection:
 Myoepithelial cells will also contract in response to vasopressin
 Milk ejection may be a condition response
 Stimulation of the genital tract such as vaginal distention causes
release of large amounts of oxytocin
 The mechanical tap stimulus does not involve oxytocin

Effect of stress on milk ejection
 Various stressful stimuli that inhibit milk ejection are associated
with increased activity of the sympathetic nervous system.
 Role of autonomic nervous system
 Sympathetic
nerves,
sympathetic nerves are:
 Epinephrine
 Norepinephrine
The
neuroendocrine
components
of

Colostrum production
 Colostrum has larger amounts of specific proteins than milk:
 Immunoglobulins
 Antimicrobial peptides (lactoferrin and lactoperoxidase)
 Other bioactive molecules, including growth factors
 Under certain circumstances, the maternal antibodies may attack
and
destroy
the
isoerythrolysis).
newborns
red
blood
cells
(neonatal

Immunoglobulin transport in the mammary gland
 The IgGs make up the majority of immunoglobulin in cow
colostrum.
 Most of the IgA and IgM that are transported into colostrum are
synthesized by the plasma cells (B lymphocytes).
 Transport of the immunoglobulins occurs through the epithelial
cells by a process involving small transport vesicles.

Immunoglobulin transport in the mammary gland

Bioactive factors in colostrums and milk
 Colostrum and milk contain many factors that can influence cell
growth, differentiation, and function:
 Glutamine
 Polyamines
 Nucleotides

Galactopoeisis
 Galactopoeisis is the maintenance of lactation once lactation has
been established.
 Two key interrelated components for maintenance of lactation:
 Galactopoietic hormones
 Prolactin
 Growth hormone
 Removal of accumulated milk

Galactopoeisis
 Role of local mammary factors in regulating milk secretion.
 Feedback inhibitor of lactation (FIL) found in milk.
 FIL is thought to be produced by the mammary cells as they
synthesize and secrete milk.

Physiology of mammary gland during the dry period
 During dry period the gland has three distinct functional states:
 The period of active involution
 The period of steady state involution
 The period of lactogenesis and colostrogenesis:
 Regeneration and differentiation of secretory epithelial cells
 Selective transport and accumulation of immunoglobulin
 The onset of copious secretion

Physiology of mammary gland during the dry period
 The mammary gland undergoing transition at two stages:
 At the beginning of the dry period
 At the end of the dry period

Physiology of mammary gland during the dry period
 Reducing the length of the dry period of dairy cows may affect:
 Postpartum health
 Reproduction performance
 Milk production

Physiology of mammary gland during the dry period
 Intra-alveolar pressure triggers the events of active involution:
 The appearance of lysosomes in the secretory epithelial cells.
 Macrophages enter the mammary tissue and secretion.
 The rate of synthesis of major milk constituents decrease:
 Fat
 Casein
 Lactose *
 Citrate *
 β-lactoglobulin
 α-lactalbumin

Physiology of mammary gland during the dry period
 By 7 days involution, the concentration of serum proteins in
mammary secretion is significantly elevated.
 The permeability barriers are not totally destroyed and the
mammary gland maintains a degree of control.

Physiology of mammary gland during the dry period
 The concentration of the iron biding protein lactoferrin (Lf)
dramatically increase.
 The major site of synthesis of the Lf found in bovine mammary
secretions is thought to be the secretory epithelial cell.
 Lf is a major protein in the secretion of the non-lactating
mammary gland.
 Lactoferrin is bacteriostatic by virtue of its ability to bind iron
with great affinity.

Development of the Mammary Gland (Mammogenesis)
 Mammary gland has allometric and isometric growth
The development of mammary growth has five phases:
 Fetal phase
 Prepubertal phase
 Postpubertal phase
 Pregnancy
 Lactation

Development of the Mammary Gland (Mammogenesis)
Timeline for the development of the mammary gland in bovines
Day 30, condensing ectodermal cells
Day 35, mammary line
Day 43, mammary bud
Day 65, teat development
Day 80, sprout
Day 150, channel formation

Development of the Mammary Gland (Mammogenesis)

Development of the Mammary Gland (Mammogenesis)
 Prepubertal mammary growth begins as isometric growth, and
before puberty becomes allometric.
 A large portion of mammary growth before puberty is an
increase in:
 Connective tissue
 Ductal growth
 Growth of the fat pad

Development of the Mammary Gland (Mammogenesis)
 Feed restricted heifers have >30% larger mammary glands at
puberty.
 Feeding high energy diets during the prepubertal period
suppresses serum bovine somatotropin (bST) levels.

Development of the Mammary Gland (Mammogenesis)
 Through the first several estrous cycles after puberty, rapid
mammary growth continues.
 Most of the growth is lost through regression during the luteal
phase of each estrous cycle.
 Nutrition plays an important, though controversial, role in
postpubertal mammary development.

Development of the Mammary Gland (Mammogenesis)
 Mammary growth is a continuous, exponential process from
conception to parturition
 The greatest increase occurs in mass of parenchymal tissue in
late pregnancy.
 The increasing udder size during the fifth and sixth months of
pregnancy is due to:
 The elongation of mammary ducts
 The formation of alveoli
 The reduction of identifiable fat cells in the fat pad

Development of the Mammary Gland (Mammogenesis)
 Mammary growth continues in early lactation.
 Persistency of lactation (maintaining peak milk yield) depends
on the continual survival of those milk-secreting cells.
 In rats, increases in total mammary DNA was seen from
parturition until weaning.

Hormonal control of mammogenesis
 The ovarian steroids are important for mammogenesis.
 The ovarian activity appears to mediate the actions of GH, specifically
through changes in IGF-I.
 During cyclic activity, there is no significant exposure to
estrogens and progesterone together.
This takes place during late pregnancy when the CL produces large
amounts of progesterone and the feto-placental unit generates elevated
levels of estrogens.

Hormonal control of mammogenesis
 In vitro studies showed that estrogen plus prolactin and growth
hormone stimulated mammary growth.
 Subsequently, estrogen was observed to induce secretion of
growth factors from pituitary, kidney, and mammary tumor cells.
 Thus,
it
was
postulated
that
growth
factors
secreted
from
extramammary tissues into serum may act via an endocrine mechanism
to mediate the mammogenic effects of estrogen.

Hormonal control of mammogenesis
 Growth factors secreted locally from mammary tissue may
mediate, via a paracrine or autocrine mechanism, estrogen effects
on mammogenesis.
 Prolactin was discovered to be critically important for initiation
of lactation in the periparturient period in several species, including
cattle.
 Indeed in cattle, lactogenesis is the only function of prolactin clearly
established to this day.

Hormonal control of mammogenesis
 Mammogenesis depends not only on hormonal concentration but
also on:
 Receptor availability within the mammary tissue
 The presence of transport proteins and intracellular lipids that are
capable of making steroids unavailable to the tissues.

Hormonal control of mammogenesis
 Several other hormones play a permissive and supportive role in
mammary growth:
 Placental lactogens
 Adrenal gland hormones
 Thyroid hormones
 Relaxin
 Parathyroid hormone
 Effect of parathyroid hormone-related protein (PTHrP)

Hormonal control of mammogenesis
 Other factors that may affect mammogensis:
 Insulin-like growth factors (IGF)
 Epidermal cell factors (ECF)
 Transforming growth factors (TGF)
 Fibroblast growth factors (FGFs)