Hormones Control of
Lactogenesis and Galactopoiesis
Hormone Levels at Calving
Blocking Prolactin Secretion
Prolactin Effects on Lactation
Effect of Prolactin Secretion on Milk
Yield
In Vitro Lactogenesis
Alpha Lactalbumin in Bovine Tissue
2.0
1.8
1.6
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
Control
Corti sol
PRL
Corti sol+PRL
Control contains insulin and T3.
Modifi ed from: G.T. Goodman, R.M. Akers, K.H. Friderici and H.A. Tucker. Endoc rinology
112:1324, 1983.
ng/ml media/mg tissue/hour
Progesterone on Lactogenesis
Alpha Lactalbumin by Bovine Tissue
3
- PRL
+ PRL
2
1
0
0
10
100
1000
Proge s terone (ng/m l)
Control contains insulin,cortisol and T3.
Modifi ed from: G.T. Goodman, R.M. Akers, K.H. Friderici and H.A. Tucker. Endoc rinology
112:1324, 1983.
GH on Lactogenesis
Alpha Lactalbumin Production
5
ng/ml media/mg tissue/h
4
3
- Prl
+ Prl (100 ng/ml)
2
1
0
0
10
100
1000
Growth Hormone (ng/ml)
Modifi ed from: G.T. Goodman, R.M. Akers, K.H. Friderici and H.A. Tucker. Endoc rinology
112:1324, 1983.
Hormone Priming on Lactogenesis
Bovine Tissue In Nude Mice
Alpha lactalbum (microgram/mg DNA)
150
100
Saline
F+Prl
50
0
Saline
E+P
Priming (20 days)
From:Sheffield, l.G. and C.W. Welsch, J. Dairy Sci, 71:75-83, 1988.
Extracellular Matrix on Lactogenesis
20
Mouse Mammary Epithelial Cells
Beta Casein
15
10
- Prl
+ Prl
5
0
-EGF
+ EGF
Culture Prior to Lactogenesis
Laminin
Model of Lactogenesis
Pregnancy
Estrogen, Progesterone
Lactation
Cortisol, Prolactin
Progesterone
Low
Progesterone
Direct +
indirect
effects
TGFa
Grow th
P4 receptor
Inhibits
Lactation
ECM
Synthesis
Epithelial
cell
Laminin-Rich
Basem ent Membrane
Milk
Milk Protein,
Other Genes
Low
P4 receptor
Epithelial
cell
Laminin-Rich
Basem ent 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 oxytocincontaining 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
Oxytocin Release at Milking
30
25
20
15
10
5
0
-25 -20 -15 -10 -5
Premilking Stimulus
0
5
10 15 20 25 30
MINUTES
Machine on
Prolactin Concentration at Milking
Alveolus Stained to Show
Myoepithelium
Myoepithelial
Cell
Milk Letdown Reflex
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
Adrenal Medulla
Posterior Pituitary
Udder Vasculature
Ihnibits
oxytocin
release
Inhibits
Blood
Flow
Epinephrine
Myoepithelium
Inhibits
Contraction
Medulla
Adrenal
Milking Apparatus
Teat Cup Structure
Milking Stimulus and Oxytocin Release
Udder Stimulation on Milk Flow Rate
5
Milk Flow (kg/min)
Stimulus
4
3
2
No Stimulus
1
0
0
1
2
3
4
5
6
Minutes Since Machine On
7
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