1. The document discusses milk synthesis and lactation in mammals. It describes the anatomy and physiology of the mammary gland and the processes of lactogenesis, galactopoiesis, and milk synthesis. 2. Lactogenesis involves the differentiation of mammary epithelial cells from a non-secretory to a secretory state in two stages: initial cytological changes and limited milk synthesis before birth, followed by copious milk secretion around the time of birth. 3. Milk synthesis occurs through the uptake of nutrients from blood by the mammary epithelial cells, which synthesize milk components like proteins, lactose, and fat within the cells and secrete them into the alveolar lumen for removal as milk.

1. Assignment
Topic: Milk synthesis and lactation
Submitted to:
Dr.Asim faraz
Submitted by:
M.Irfan shahid
Roll no. 26(M)
Semester : 6th

2. Milk synthesis and lactation
Mammary gland:
Milk production units of the mammals is known as
mammary gland ex: cattle has four mammary glands.
Number of mammary glands in different species
Anatomy and Physiologyof Mammary gland:
The mammary gland of the
dairy cow is composed ofmillions of milk-producing alveoli, which convert blood
components into protein, fat, and lactose. The gland is attached to the bodyby the
median and lateral suspensoryligaments. Milk exits each mammary gland via a

3. teat equipped with a teat canal. Nutrients are brought to mammary tissue by the
mammary artery, which passes through the inguinal canal to the dorsalsurface of
the udder, ending in capillaries that supply milk precursors to alveoli. After the
interchange between blood and tissue, blood reaches the small veins, which run
dorsally and unite to form the mammary veins at the base of the udder. Interstitial
fluids originating from capillaries that nourish milk-producing cells recirculate via
the lymphatic system, which carries waste products away from the udder. The
major nerves are the sensorynerves that carry impulses from the four quarters and
teats to the brain. The nervous system has no direct involvement in the production
of milk or removal from the udder, but it is essential to the milking process by
triggering mechanisms of hormone release from the brain to the mammary tissue.
Lactogensis:
is the term meaning the initiation of lactation. This it the process of
functional differentiation which mammary tissue undergoes when changing from a
nonlactating to a lactating state. This process is normally associated with the end of
pregnancy and around the time of parturition. Because lactogenesis is particularly
dependent upon a specific set of hormones (called the Lactogenic Complexof
hormones), mammary tissue from most states of the nonlactating mammary gland
also can be made to undergo some degree of lactogenesis by administration of high
amounts of those hormones, even in nonpregnant animals.

4. Defining Principles of Lactogenesis:
Lactogenesis is a series of cellular changes whereby mammary epithelial cells are
converted from a nonsecretory state to a secretory state.
Lactogenesis is a two stage process:
1. Cytologic and enzymatic differentiation of alveolar epithelial cells. This
coincides with very limited milk synthesis and secretion before parturition.
Cytological changes associated with stage 1 of lactogenesis are described below.
Enzymatic changes include increased synthesis of acetyl CoA carboxylase, fatty
acid synthetase, and other enzymes associated with lactation, and increases in
uptake transport systems for amino acids, glucose, and other substrates for milk
synthesis. Note that synthesis of a-lactalbumin, and therefore, lactose synthesis
does not begin until stage 2 of lactogenesis. Stage 1 of lactogenesis coincides with
the formation of colostrum and immunoglobulin uptake (see The Neonate and
Colostrum sections).
2. Copius secretionof all milk components. In the cow this begins about 0-4 days
before parturition and extends through a few days postpartum. It is not until the
release of the inhibitory effects of progesterone on lactogenesis (about 2 days
prepartum in many mammals) and the stimulation by the very high blood
concentrations of prolactin and glucocorticoids associated with parturition, that
copious milk secretion begins (stage 2 of lactogenesis).
Milk synthesis process:
The precursors of milk components leave the blood and enter
the extracellular fluid between the capillaries and the epithelial cells.
Precursors then are taken up from the extracellular fluid through the
basolateral membrane of the epithelial cell. Once inside the cell the precursors
enter the appropriate synthetic pathway. In addition, some pre-formed
proteins, suchas immunoglobulins, are transported intact through the cell.
There are 5 routes by which milk precursors orcomponents enter milk in the
alveolar lumen, including uptake of amino acids, uptake of sugars and salts,
uptake of milk fat precursors, uptake of preformed proteins
(immunoglobulins, and the paracellular pathway. The diagram below
indicates the mechanisms of uptake and utilization of amino acids for protein
synthesis, glucose for lactose synthesis, fatty acids and glycerol for milk fat

5. synthesis, immunoglobulins for transport across the cells, and the paracellular
pathway.
Amino acids to proteins: Amino acids are absorbed through the basal
membrane of the cell by several specific amino acid transport systems. Once
inside the cell, amino acids are covalently bound together to form proteins at
the polysomes (poly-ribosomes) on the rough endoplasmic reticulum (RER).
Proteins that are synthesized at the RER include the proteins to be secreted
(such as the milk proteins casein, ß-lactoglobulin, and a-lactalbumin) and
membrane bound proteins (such as proteins involved in cell-cell contacts and
membrane bound enzymes). Newly synthesized proteins are transferred from
the RER to the Golgi apparatus where they are processed fortransport out of
the cell. Remember that casein is secreted as a micelle; the micelle is formed
in the Golgi from the casein molecules, calcium and phospohorous. Caseins
and other proteins undergo post-translational processingin the Golgi. Proteins
that remain in the cell are synthesized by the ribosomes in the cytoplasm;
these would include all the cellular enzymes, structural proteins in the cells
such as keratin, and all other cellular proteins.
Milk proteins and lactose are transported to the apical membrane of the cell
via secretory vesicles that bud off of the Golgi; these secretory vesicles are
bounded by a lipid bilayer membrane. These secretory vesicles make their
way to the apical membrane by a mechanism involving microtubules (made
of polymerized tubulin). Tubulin is one of several cytoskeletal proteins which
form the cellular scaffolding, providing the cell with structure; keratin is
another cytoskeletal protein. The secretory vesicles do not transfer to the
basolateral membrane. At the apical membrane, the membrane of the
secretory vesicle fuses with the inner surface of the apical membrane,
resulting in an opening through which the vesicle contents are discharged into
the alveolar lumen.
Glucose to lactose : Glucose enters the cell via the basolateral membrane via
a specific transport mechanism. Some glucose is converted to galactose. Both
glucose and galactose enter the Golgi and enter into a reaction resulting in
formation of lactose (see Lactose Lesson). The formation of lactose in the
Golgi results in drawing water into the cell, into the Golgi, and ultimately
becoming part of milk. Note that the Golgi apparatus is involved in

6. processing of milk proteins, synthesis of lactose, and the osmotic draw for
water. The Golgi apparatus is very important to the synthesis of skim milk
components. Note that lactose (and therefore much of the water of milk) is
secreted via the secretory vesicles along with the milk proteins.
Milk fat precursors to milk fat : Precursors of milk fat synthesis are also
taken up by the epithelial cells at the basolateral membrane. Acetate and ß-
hydroxybutyrate are important precursors of fatty acid synthesis in mammary
cells in some species (ruminants, especially). These precursors are absorb
through the basolateral membrane. In addition, preformed fatty acids,
glycerol, and monoacylglycerides are absorbed at the basolateral membrane.
All these components enter into the synthesis of triglycerides of milk (see
milk Fat Lesson). Milk fat triglycerides are synthesized on the smooth
endoplasmic reticulum (SER) and form small droplets. Numerous small lipid
droplets will fuse together as the growing lipid droplet moves toward the
apical membrane. At the apical membrane the large lipid droplet forces out
the apical membrane of the cell, the apical membrane surrounds the lipid
droplet until it pinches off and enters the lumen. [Imagine standing inside a
balloon and trying to punch your hand through the balloon's wall. The
balloon's wall would wrap around your hand.] So, in the lumen of the
alveolus, the milk fat globule (or milk lipid globule as it is now called) is
surrounded by a membrane. This membrane originally was part of the
epithelial cell's apical membrane. Note that INSIDE the cell the lipid is NOT
membrane bound and is called a lipid droplet, while after secretion in the
LUMEN, the milk lipid globules are surrounded by a membrane.

7. Transport of Milk Components Not Synthesized in the Epithelial Cells :
A number of other components pass across the epithelial cell barrier
essentially unchanged from their form in the blood. These
include immunoglobulins which bind to specific receptors on the basolateral
surface of the cells, are taken "into" the cell in endocytic vesicles, and are
transported to the apical side of the cell via the endocytic vesicles
(or transport vesicles), where the membrane of the transport vesicles fuses
with the inner surface of the apical membrane of the cell and releases the
immunoglobulin into the lumen of the alveolus. As the transport vesicles
traverse the cell they do not seem to interact with the Golgi, secretory vesicles
or the lipid droplets. Some serum albumin may be transported across the
epithelial cells by this mechanism. There is not a serum albumin receptor,
however, serum albumin molecules probably are internalized into the cell
along with the immunoglobulins which are taken up by the transport vesicles.
ParacellularPathway: Because of the tight junctions between epithelial
cells, there is little or no "flow" of anything between the cells, except perhaps
water and some ions. Anytime something passes between the cells through
the tight junction, this is called the paracellular pathway. When the udder is
inflamed, such as during mastitis or involution, or when oxytocin is causing

8. milk ejection, the tight junctions open some or become 'leaky'. This allows
lactose and potassium to move from the lumen into the extracellular space,
and for sodium and chlorine to move into the lumen from the extracellular
space. This results in a change in electrical conductivity of the milk (as used
in detecting mastitis), as well as an increase in concentrations of lactose and
other milk-specific components in the blood. Lactosecan be measured in the
urine of a cow during the peripartum period. Milk proteins can be detected in
the cow's blood during lactation and early involution.
Other components that can enter the lumen without passing through the
epithelial cells are leukocytes (discussed in Mastitis Module). The leukocytes
comprise the vast majority of the somatic cells in the milk. These cells pass
between the epithelial cells and in the process they "break open" the tight
junctions between the epithelial cells and enter via the paracellular pathway.
Of course, this also allows other extracellular components like salts to diffuse
into the lumen and milk components to diffuse out of the lumen into the
extracellular fluid. [This is one reason why there is a change in electrical
conductivity in the milk during mastitis.
Glactopoesis:
Galactopoiesis is the maintenance of lactation once lactation has been
established. Two key interrelated components contribute to the maintenance
of lactation, galactopoietic hormones and removal of accumulated milk.
Because of the importance of galactopoietic hormones in milk production,
sometimes the word galactopoiesis also is used to indicate enhancement of
lactation, especially in dairy animals. Inhibition of secretion of key
galactopoietic hormones will depress milk production to varying degrees
depending on the species, stage of lactation, and the particular hormone being
suppressed. Therole of galactopoietic hormones such as prolactin in
maintenance of lactation is well established. Prolactin is released at the time
of milk removal in ruminants and nonruminants, and it remains a key
systemic modulator of milk secretion during lactation. Conversely, growth
hormone is generally considered to be the predominant galactopoietic
hormone in ruminants. Inhibition of prolactin secretion or administration of
prolactin to lactating cows has little effect on milk yields.
Regardless of the hormones involved, all attempts to evaluate milk secretion

9. must account for continued removal of milk. This is a reminder of the critical
role of local mammary factors in maintenance of milk secretion. One such
factor that plays a major role in regulating milk secretion in many species is a
feedback inhibitor of lactation (FIL) found in milk. FIL is thought to be
produced by the mammary cells as they synthesize and secrete milk.
Accumulation of FIL in the milk-producing alveoli results in feedback
inhibition of milk synthesis and secretion.
Frequent removal of milk from the gland minimizes local inhibitory effects of
FIL and increases milk secretion. Milk removal involves several mechanisms
that impact milk production, including removal of local inhibitory
components, regulation of local blood flow, and even physical factors in the
alveolus. The effects of frequency of milk removal are tied closely with the
local regulation of milk secretion.