lactation physiology (part 1) by: a. riasi (phd in animal nutrition & physiology)...

Lactation Physiology(part 1)

By: A. Riasi (PhD in Animal Nutrition &

Physiology)

فیزیولوژی تولید و ترشح شیر

At the end of this section student will be able to reply

What is the supportive system in udder?

What is the forstenberg’s rosette in papilla mammae?

What are the improtant parts of a secretory cells?

Which barriers are between the circulatory primary substance and milk?

What are the transporter systems in mammary epithelial cells?

Where is the lactose production site in the alveolar epithelial cells?

What are the pathways for milk fat globule transit and secretion from

mammary epithelial cells?

How is the de novo fatty acid synthesis in mammary cells?

What is the milk fat depression syndrome?

What is a mammary gland?

Is modified sweat gland.

Serves a reproductive function; nourishment of the neonate.

Can repeatedly undergo growth, functional differentiation, and

regression.

Relies on same endocrine (hormonal) support for development

and function.

Example: gonadal steroids, prolactin, etc.

What is the difference between the animal udder?

SpeciesAnterior

(thoracic)Intermediate(abdominal)

Posterior(inguinal)

Total

Goat, sheep, horseguinea pig

0022

Cattle0044

Cat2248

Dog422 or 48 or 10

Mouse60410

Rat62412

Pig66618

proboscideans, primates2002

www.wikipedia.org

What is the difference between the animal udder?

Cow: Four glands and four teats

Sheep and goats: Two glands and two teats

Sow: 12-14 teats and two glands per teat.

Mare: Four glands and only two teats.

The udder is a complex system

A supportive system.

A secretory system composed of epithelial cells.

A duct system for storage and conveyance of milk.

Blood, lymph, and nerve systems.

The udder of cows

The weight of empty cows udder is about 12-30 kg.

The udder weight is affected by:

Age

Stage of lactation

Amount of milk in the udder

Inherited differences among cows

The supportive system of udder

There are seven tissues that provide support for the udder:

Skin (covering the gland is only of very minor support)

Superficial fascia or Areolar subcutaneous tissue

Coarse areolar or cordlike tissue

Subpelvic tendon

Superficial layers of lateral suspensory ligament

Deep lateral suspensory ligament

Median Suspensory Ligament

An illustrated view of the ligaments that permit udder suspension (Courtesy of Iowa State University)

Teat structure

Furstenburg’s rosette

Annular (cricoid) rings

Interior anatomy of the Mammary Gland

The interior structure of mammary gland:

Connective tissue (Stroma)

Ductular system

Secretory tissue

Mammary duct system

Secretory tissue

(Adapted from Akers & Denbow, 2103)

Mammary alveolus. This diagram illustrates the three dimensional structure of the mammary alveolus. The hollow center of the alveolus provide a space for the accumalation of milk components that have been synthesized and secreted by the secretory cells that compose the internal wall of the structure. The outside of the alveolus has a network of myoepithelial cells that contract in response of release of oxytocin at the time of milking. This forces stored milk into the terminal duct, which exits the lumen the alveolus. The milk progresses through larger ducts to be emptied at the nipple or teat end. (Adapted from Akers & Denbow, 2103)

A photomicrograph of a developing mammary duct. Taken from a Holstein calf, this tissue stained with specific cytokeratin 18 (red, a marker specific for epithelial cells), CD10 (green , a marker of myoepithelial cells), and Ki67 (yellow, a protein produced in nuclei of cells that are about to divide). The tissue section is from a study to evaluate the effects of the ovary on ontogeny of myoepithelial cells in the bovine mammary gland. (Adapted from Akers & Denbow, 2103)

Secretory tissue

A lactating secretory cell is the basic unit of milk synthesis

Milk precursors are taken from the blood into the cell

The secretory cell have two kind of junctions with neighbor cells:

Tight junction around the apical portion

Gap junction in lateral portion

Major component of a secretory epithelial cell

Nucleus

Rough Endoplasmic Reticulum

Golgi apparatusSecretory vesicles

Lysosomes

Cytoplasm

Tight junctionGap junction

Basal and lateral membranes

Apical membrane

Basement membrane

Smooth Endoplasmic Reticulum

Milk synthesis and secretion

The product of mammary gland depends on two mode of

secretion:

Apocrine

Merocrine

Other components are derived by passage of soluble molecules

across (transcellular) and sometimes between (paracellular) the

cells.


Physically, milk is a complex solution of:

salts,

carbohydrates,

miscellaneous compounds with dispersed proteins and protein

aggregates,

casein micelles, and

fat globules.

Milk osmolarity generally equals blood (~300 mOsm) and has a

pH between 6.2 and 7.0.


Function of the mammary gland during established lactation is

closely linked with a number of hormones, growth factors, and

local tissue regulators.

Along with mammary cell-specific constituents, milk contains a

myriad of minor components.

Many of these molecules are important nutrients or regulators of

the neonate.


Molecules are transported into the milk by several possible

routes.

Mammary epithelial cells are able to maintain substantial

gradients for Na+, K+, and Cl− ions across the cell membrane.

Concentrations of Na+ inside (~ 43 mM) the cells are typically

lower than outside (150 mM)

The gradient for K+ is the opposite (143 mM inside compared

with 4.5 mM outside).

Concentration of Cl− is higher inside the cells.


Milk is a rich source of calcium.

The calcium in the milk exists as:

Casein-bound calcium

Calcium associated with various inorganic anions

For example, citrate and phosphate

Free calcium


The rate of calcium influx into the cell is matched by a

corresponding uptake of calcium by cellular organelles.

An ATP-dependent calcium pump on Golgi membranes

The uptake of Ca by the epithelial cells probably dependent to:

Parathyroid hormone-related protein

1,25-(OH)2 vitamin D3.

Precursors of Milk

Precursors of milk come from the bloodstream and the primary

substrates extracted from blood are:

Glucose

Amino acids

Fatty acids

Minerals

Acetate *

βHB *

Precursors of Milk

Several materials in milk come unchanged from the blood:

Minerals

Hormones

Immunoglobulins

Synthesis of milk proteins

There are several specific systems for amino acids absorption

through the basal membrane.

Inside the cell, amino acids are covalently bound together to

form proteins at the polysomes (Poly-ribosomes).

Proteins sythesized at RER include:

Casein

β-lactoglobulin

α-lactalbumin

Membrane bound proteins

Membrane boding enzymes

Synthesis of milk proteins

Synthesized proteins are transferred the golgi apparatues (GA).

Casein is secreted as micelle, which is formed in the GA from:

Casein molecules

Calcium

Phosphorus

A: a submicelle; B: protruding chain; C: Calcium phosphate; D: κ-casein; E: phosphate groups

Synthesis of milk lactose

Glucose enters the cells via the basolateral membrane by

specific transport system.

Some glucose is converted to galactose in the cell.

Both glucose and galactose enter the GA and react resulting in the

formation of lactose.

Synthesis of milk fat

The sources of milk FA:

Blood FA

De novo FA

Glycerol

Monoacylglyceride (MAG)

Acetate and *

β-hydroxybutyrate *

Milk fat triglycerides are synthesized on the smooth

endoplasmic reticulum and form small droplet.


The protein coat on the milk fat globule membrane comprises:

Mainly butyrophilin (BTN) *

Xanthine oxidoreductase (XDH) *

Adipophilin (ADPH)**

Mucin 1

CD36

Periodic acid/Schiff

PAS III

FABP

Pathways for milk fat globule transit and secretion from mammary epithelial cells


The properties of milk fat:

Milk fat composed of different fatty acids:

Short chains (4-8 C)

Medium chains (10-14 C)

Long chains (≥16 C)



TAG (more than 95% of milk fat)

DAG (2%)

Phospholipids (1%)

Cholesterol (0.5%)

FFA (0.1%)

Ether lipid, Fat soluble vitamns., etc.



Saturated FAs (~70%)

Palmitic acid

Myristic acid

Stearic acid

Monounsaturated FA (~25%)

Oleic acid

Vaccenic acis

Polyunsaturated FA (~5%)


There are two sources of FA for milk fat synthesis:

The de novo FA synthesis in mammary epithelial cells

Short chain (4-8 C)

Medium chain (10-14 C)

~ 50% of 16 C

Preformed FA uptake from blood circulation

~ 50% of 16 C

> 16 C

De novo fatty acid synthesis

In ruminants, the substrates for de novo FA synthesis in

mammary epithelial cells are:

Acetate produced by rumen fermentation

β- hydroxybutyrate produced by the rumen epithelium

Preformed fatty acid uptake

Long-chain FA taken up by the mammary gland are imported

from plasma:

Released from circulating lipoproteins by lipoprotein lipase

NEFA bound to albumin

There is evidence showing that the membrane transport of long-

chain FA is a facilitated process.

Some factors might play a role in FA uptake and transport:

Cluster of differentiation 36 (CD36)

Fatty acid binding protein 3 (FABP3)

Properties of milk TAG

Fatty acids are not esterified randomly to the sn-1, -2, and -3

positions of glycerol backbone.

The distribution of FA is dependent on the distinct binding

affinities of the acyltransferase enzymes for substrate FA.

Adapted from McManaman and Neville, 2003

Abbreviations: SV, secretory vesicle; RER, rough endoplasmic reticulum; BM, basement membrane; N, nucleus; PC, plasma cell; FDA, fat depleted adipocyte; JC, junctional complex containing the tight and adherens junctions; GJ, gap junction; ME, myoepithelial cell.

Transport of milk components


Pathway I depicts exocytotic for:

Protein secretion by alveolar cells

Water

Lactose

Oligosaccharides

Phosphate

Calcium

Citrate


Pathway II depicts milk fat secretion.

Milk lipids, primarily triacylgycerides and phospholipids, are

synthesized in the smooth endoplasmic reticulum in the basal region

of the cell.

Newly synthesized lipid molecules form cytoplasmic lipid

droplets and are secreted by a unique budding process (MFGs).


Milk fat globule membrane is known to contain numerous

enzymes, including oxidases, reductases and hydrolases with

relatively high specific activities.

In particular milk fat globule membranes are highly enriched in

the purine oxidizing enzyme xanthine oxidoreductase (XOR).


Pathway III depicts transcytotic pathways for transport of

proteins and other macromolecules.

Transcytotic secretion of immunoglobulin A in rabbit mammary

glands has been shown to occur.

Prolactin and transferrin transcytosis have been detected

Transfer of labeled low-density lipoprotein (LDL) from blood to

milk has been reported.

Considering that xenobiotic agents, including carcinogens and some

drugs, can bind to and be transported by lipoproteins.


Pathway IV depicts transport of:

monovalent and polyvalent ions

glucose

amino acids


Ion transport: Transporters or channels for sodium, potassium and

chloride have been identified on the basal and apical plasma

membranes of alveolar cells.

Phosphate and iodide transporters appear to be limited to the basal

membrane.


Glucose transport: Glucose transport systems have been detected

in the mammary gland at both the apical and basal plasma

membrane, and on Golgi and secretory vesicle membranes.

Two distinct glucose transport mechanisms have been identified

in the mammary gland:

GLUT1 transporter mechanism

A sodium dependent glucose transporter


Amino acid transport: Both sodium-dependent and sodium

independent amino acid transport mechanisms analogous to those

found in other organs have been demonstrated at the basolateral

component of the mammary epithelium.

Other agents: The presence of higher than expected

concentrations of certain drugs in milk have raised the possibility

that alveolar cells may have active transport mechanisms for such

compounds.


Pathway V depicts transport the paracellular pathway for direct,

bi-directional, extracellular movement of both low-molecular-weight

substances and macromolecular solutes.

This pathway is closed during lactation in humans and most other

species by the presence of very tight-junction.

Milk fat depression (MFD)

Several theories have been proposed to explain the physiology

behind this reduction in fat synthesis.

Lower production of acetic and butyric acids in the rumen caused

less fat production in mammary gland.

The greater proportionate production in rumen increases the blood

insulin, which partitions nutrients away from the mammary gland.

A more current theory is that the combination of high grain and

high unsaturated fatty acids in the diet causes the microorganisms in

the rumen to produce more trans fatty acids.

Milk fat depression (MFD)

Avoiding milk fat depression

Proper cooling of cows

Control the amount of polyunsaturated fatty acids in the diet

Balance dietary carbohydrates

Buffer and alkalinizing agents

Ionophores

Feeding Management

lactation physiology (part 1) by: a. riasi (phd in animal nutrition & physiology)...

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