Hormones Control of Lactogenesis and Galactopoiesis

Hormones Control of
Lactogenesis and Galactopoiesis

Hormone Levels at Calving

Blocking Prolactin Secretion

Prolactin Effects on Lactation

Effect of Prolactin Secretion on Milk
Yield

2.0
1.8
1.6
1.4
1.2
In Vitro Lactogenesis
Alpha Lactalbumin in Bovine Tissue
1.0
0.8
0.6
0.4
0.2
0.0
Control Cortisol PRL Cortisol+PRL
Control contains insulin and T3.
Modified from: G.T. Goodman, R.M. Akers, K.H. Friderici and H.A. Tucker. Endocrinology
112:1324, 1983.

Progesterone on Lactogenesis
Alpha Lactalbumin by Bovine Tissue
3
2
1
0
Control contains insulin,cortisol and T3.
- PRL
+ PRL
0 10 100 1000
Progesterone (ng/ml)
Modified from: G.T. Goodman, R.M. Akers, K.H. Friderici and H.A. Tucker. Endocrinology
112:1324, 1983.

ng/ml media/mg tissue/h
5
4
3
2
1
0
GH on Lactogenesis
Alpha Lactalbumin Production
0 10 100 1000
Growth Hormone (ng/ml)
- Prl
+ Prl (100 ng/ml)
Modified from: G.T. Goodman, R.M. Akers, K.H. Friderici and H.A. Tucker. Endocrinology
112:1324, 1983.

Hormone Priming on Lactogenesis
Alpha lactalbum (microgram/mg DNA)
150
100
50
0
Bovine Tissue In Nude Mice
Saline E+P
Priming (20 days)
Saline
F+Prl
From:Sheffield, l.G. and C.W. Welsch, J. Dairy Sci, 71:75-83, 1988.

Extracellular Matrix on Lactogenesis
Beta Casein
20
15
5
0
Mouse Mammary Epithelial Cells
10 - Prl
+ Prl
-EGF + EGF Laminin
Culture Prior to Lactogenesis

Model of Lactogenesis
Pregnancy Lactation
Estrogen, Progesterone
Direct +
indirect
effects
TGFa
Growth
Epithelial
cell
Progesterone
P4 receptor
Inhibits
Lactation
ECM
Synthesis
Laminin-Rich
Basement Membrane
Cortisol, Prolactin
Low
Progesterone
Milk
Epithelial
cell
Milk Protein,
Other Genes
Low
P4 receptor
Laminin-Rich
Basement Membrane

Hormonal Regulation of Lactation

Effects of Estrogen and Progesterone
on Lactation

Hormonal Maintenance of Lactation

Hormones and the Maintenence of
Lactation

Insulin and Growth Hormone
Throughout Lactation

Growth Hormone Levels in Cattle Selected for
Higher Milk Production vs. Control Cattle

Prolactin Throughout Lactation

Insulin, Growth Hormone and Cortisol
Through Lactation

Oxytocin
• Oxytocin is a 9 amino acid long peptide. The
amino acid structure of oxytocin is:
• Cys-Tyr-Ile-Gln-Asn-Cys-Pro-Leu-Gly
• It has a molecular mass of 1007 daltons.
Oxytocin has a disulfide bond between the
two cysteines. Reduction of the disulfide bond
inactivates oxytocin. One IU (international
Unit) is approximately 2 micrograms of pure
peptide.

Oxytocin Synthesis
• Oxytocin is synthized in the hypothalamus in specific nuclei, the
paraventricular nucleus and the supraoptic nucleus in the hypothalamus.
[A cluster of nerve cells in the brain is often called a nucleus. This is
different from the nucleus of a single cell.] Neurons in these hypothalamic
nuclei synthesize the oxytocin precursor and package it into vesicles.
Oxytocin is initially synthesized as a large molecular weight precursor
which also consists of the oxytocin-carrier peptide neurophysin. The
precursor is proteolytically cleaved in the neuron in the oxytocin-
containing vesicle to yield oxytocin bound to neurophysin. The oxytocinneurophysin
complex is the intracellular storage form of oxytocin.
• The oxytocin-containing vesicles are transported from the cell body (which
is in the hypothalamus), down the axons to the neuron endings in the
posterior pituitary. This is called the hypothalamo-neurohypophysial tract.
The oxytocin-neurophysin complex is stored in neurosecretory granules
called herring bodies in the axon ending.

Pituitary Gland

Serum Oxytocin (µU/ml)
35
30
25
20
15
10
5
0
-25
Oxytocin Release at Milking
-20
-15
-10
-5
Premilking Stimulus
0
5 10 15 20
MINUTES
Machine on
25
30

Prolactin Concentration at Milking

Myoepithelial
Cell
Alveolus Stained to Show
Myoepithelium

Milk Letdown Reflex
Hypothalamus Posterior
Pituitary
Oxytocin
Release
Heart
Lungs
Aorta
Spinal
Cord
Myoepithelial
Cell Contraction
Alveolus
Milk
Ejection
Dorsal Root
Inguinal
Nerve
Udder
Stimulation

Milk Letdown
Alveolar Contraction

Oxytocin Release and Half-Life
• It is estimated that the bovine pituitary has about
800 micrograms of oxytocin. This is about 40X
what is in the blood under resting conditions.
Only about 1/3 of pituitary oxytocin is released at
a milking.
• Oxytocin receptors on myoepithelial cells can
respond to very low levels of oxytocin.
• Oxytocin has a short half-life in the blood = 0.55
to 3.6 min. This means that the removal of milk
by machine or by nursing must be closely timed
with stimulation of the teats.

Factors Modifying Milk Letdown
• Autonomic nervous system
– Stress gives epinephrine release
– Inhibits oxytocin release
– Inhibits myoepithelial cell contraction
– Inhibits blood flow to udder
• Conditioned reflex
– Letdown in response to sights, sounds associated
with milking

Interesting Stimulation of Milk
Letdown

Posterior Pituitary
Medulla
Adrenal Medulla
Ihnibits
oxytocin
release
Epinephrine
Adrenal
Inhibits
Blood
Flow
Inhibits
Contraction
Udder Vasculature
Myoepithelium

Milking Apparatus

Teat Cup Structure
Teat Chamber
Pulsation Chamber
Vacuum
Milk Flows
Vacuum
Liner
Air
Shell
No Milk Flow
Vacuum

Milking Stimulus and Oxytocin Release

Milk Flow (kg/min)
Udder Stimulation on Milk Flow Rate
5
4
3
2
1
0
0
1
2
3
4
Stimulus
Minutes Since Machine On
5
6
7
No Stimulus
8

Residual Milk
• Left in udder after normal milking
• About 10% of milk
• Can remove with oxytocin

Phase Separation and Residual Milk

Removing Residual Milk
• Oxytocin injections
– Expensive
– Not approved use
• Machine stripping
– High incidence of liner slips
– Increases mastitis risk
• Udder massage
– Second oxytocin release.

Udder Pressure and Milk Secretion

Milk Letdown and Mammary Pressure

Effect of Exogenous Oxytocin on Milk
Yield