1. Lactation: The final phase of mammalian reproduction
BIOL30001 Reproductive Physiology
Lactation, G Shaw
BIOL30001 Reproductive Physiology
Lactation: The final phase of mammalian reproduction
Geoff Shaw

2. References EssRep7 Chapter 18 J&E6: Chapter 14.
Hormonal control of lactation, A.Cowie in Hormonal Control of Reproduction: Austin & Short. Book 3, Chapter 8:
Physiology of Reproduction th Ed. Knobil & Neill:
Chapter 56, p.1099:Control of Mammary Gland Growth and Differentiation. W. Imagawa, J. Yang, R. Guzman & S. Nandi
Chapter 57, p.1065 :Lactation and Its Hormonal Control. H. Allen Tucker
Chapter 59, p.1131:Milk Ejection and Its Control. JB. Wakerley, G. Clarke & A.J.S. Summerlee
Lactational control of Reproduction, A.S. McNeilly, in Reproduction Fertility and Development (2001) 13:
Margaret C. Neville. (1998) Milk Secretion: an overview.

3. Lactation Primary source of nutrition and energy for newborn mammal
Immune protection
Mammary glands change – hormones and development
Variation between species: eg
number of glands: human 2; wallaby 4; pig 18; cow 4 (apposed in single udder)

4. Milk composition varies with species
Component
(g / 100 mL)
Human
Elephant Seal
Water 90 35
Protein
1.1 10
Carbohydrate
7.5 2
Lipid
4.2 55
Energy (MJ / L)
3.3 23

5. Structure of a mammary lobule
eg. cluster of alveoli in the goat
myoepithelial cells
arteriole
alveolar
epithelial cells
venule
capillaries
milk
Alveolus
milk duct
From Austin and Short 1984

6. Structure of mammary lobules and alveoli
Note vascular
supply around
alveolus
myoepithelial
cells surrounding
alveolus contract, increasing intra-mammary pressure at milk let-down
J and E, Fig 14.3

7. duct systems in different species
15-20 mammary lobes
Dilating as a lactiferous
sinus emerging at nipple
J and E Fig14.2

8. Development of mammary gland in fetal mouse
Ovariectomised
female
Normal female
Normal male
Castrated male
androgens cause regression of the mammary primordia
From Austin and Short 1984

9. Postnatal mammary growth in rat
pre-pubertal
late-pregnancy 
lactation
pubertal
Oestrogen,
progesterone, cortisol,
growth hormone,
placental lactogen and
prolactin needed for
mammary growth during
first pregnancy
post-
pubertal
From Austin and Short 1984
cyclic changes through oestrous / menstrual cycles

10. Mammary gland cycle

11. Summary: structure and development
Mammary gland:
Structure of mammary gland – variations on a theme
ducts and cisterns
alveoli open into milk ducts
ducts join and empty via nipple or teats.
galactophores are common ducts leading to teat: rabbits 6-8; man 15-20; agile wallaby approx. 20.
supernumerary teats
Fetal development
present in both sexes but poorly developed in men
Regress in male mice and rats as a result of androgens
Development after birth
full growth not achieved until end of puberty or in early lactation

12. Hormonal regulation of milk secretion differs between species
To maintain high milk production after removal of the pituitary gland:
Rats need:
Prolactin
Adrenocorticotrophin
Sheep & goats need:
Growth hormone
Prolactin
Adrenocorticotrophin*
Thyrotrophin†
Rabbits need:
Prolactin
Milk secretion requires hormonal support but
species’ needs vary
ACTH maintains cortisol secretion from the adrenal gland
† TSH maintains thyroid hormone secretion from the thyroid gland

13. Milk secretion: hormonal control
Mammary gland transplanted to the neck of a goat (Jim Linzell’s experiment)
separated from nerve supply
continued milk secretion
Control is hormonal, not neural
However milk removal
necessary for continued lactation
(Malcolm Peaker)

14. Pregnancy, hormones and milk secretion
Onset of lactation in women
Colostrum
high protein
rich in immunoglobulins
Mature milk
7% lactose
4% fat
1% protein
+minerals, vitamins etc
Two 25 mL samples of human breast milk. The left hand sample is foremilk, the watery milk coming from a full breast. The right hand sample is hindmilk, the creamy milk coming from a nearly empty breast
J & E 14.5

15. pregnancy  mammary gland development
high progesterone and oestrogens
hPL (hCS)
prolactin
peripartum  transition to lactogenesis
fall in progesterone and oestrogens
no hPL
slow fall in PRL  needs nipple stimulation (suckling) to maintain PRL and milk production

16. Local regulation FIL – Feedback inhibitor of lactation
Small protein secreted in alveolus
If not removed by emptying alveolus, it acts to suppress further milk secretion.

17. Mammary secretory processes
Milk Fat Globule
exocytosis: proteins made via RER and Golgi; Lactose
apocrine secretion of lipids; vesicle membranes  phospholipids
trans-membrane: water; small molecules; drugs
trans-cytosis: immunoglobulins; some hormones & growth factors
paracellular: immune cells; leakiness may be high in disease states increasing transfer of interstitial fluids.

18. lactation Milk secretion
Initiation of milk secretion begins in pregnancy
Prolactin and other hormones
Synthesis of milk constituents within alveolar cells
Intracellular transport of milk components
Discharge of constituents into alveolar lumen
Local control - FIL
Milk removal
Passive removal of milk from cisterns and large ducts
Stimuli
Sucking
Sights, smells, sounds, tactile stimuli associated with suckling
Reflex ejection of milk from alveoli (‘let down’ or ‘draught’)
Oxytocin

19. Milk secretion: The importance of sucking
Sucking induced release of prolactin.
Prolactin
VIP = Vasoactive intestinal peptide ,
VIP a potent Prl releasing factor
Dopamine from TIDA nerves,
- DA a Prl release inhibitory factor
EssRep7 18.6

20. The milk ejection reflex
Sucking-induced
release of
oxytocin.
EssRep7: 18.7

21. Milk ejection: Anticipation of milking on oxytocin concentrations in dairy cows
PM preparation for milking; MA application of teat cups; S stripping; C control level.
From Austin and Short 1984

22. Milk ejection: the role of oxytocin
Hottentot method of inducing milk let down (Ferguson Reflex)

23. Milk ejection: Oxytocin receptors regulate response
Oxytocin receptors during pregnancy and lactation in rat mammary gland
from Soloff and Weider 1983

24. Hormonal control of lactation:
consists of milk secretion and milk removal stages.
Maintenance of lactation usually requires several anterior pituitary hormones
prolactin is critical in non-ruminants, and growth hormone in ruminants.
Oxytocin essential for milk ejection. Milk removal essential for continued lactation
responses mediated by receptors.

25. Milk composition: Changes in peripartum period
colostrum
Milk composition
in women pre- and post-partum.
0 indicates time of
birth
From Kulski and Hartmann,
1981

26. Milk Composition:
Colostrum: post-partum secretion high in protein, sodium and chloride.
also antibodies (IgG and IgA).
Milk: large species differences in concentrations of milk fat, lactose, protein and water.
Milk fat mixture of lipids: triglycerides, diglycerides, monoglycerides, free fatty acids, phospholipids and sterols.
Arctic, aquatic, desert mammals produce milk with 75% energy in lipid fraction
Frequent nursing species produce milk with lower nutrient density

27. Lactation in marsupials
Lipids
Proteins
Carbohydrates
Milk composition changes in marsupials
From Green 1984

28. Milk ejection in the agile wallaby - concurrent asynchronous lactation
difference in response to OT allows milk ejection in gland with PY continuously attached
sucking by young at foot causes ME in both glands
intra-mammary pressure
from Lincoln and Renfree 1981

29. Prolactin related suppression of reproductive cycle
sucking
stimulus
Dopamine and agonists (bromocriptine) inhibit prolactin synthesis.
High levels of Prolactin in lactation inhibits GnRH.
pituitary LH response to GnRH reduced, failure of positive feedback
ovarian response to LH same.
naloxone (opiate inhibitor) also inhibits prolactin release (alternate pathway)
nipple
spinal cord
hypothalamus
β-endorphin release - -
dopamine release
GnRH pulse generator
oxytocin -
prolactin
milk production
lactational
infertility
milk
ejection

30. Contraceptive effects of breastfeeding
Non lactating, no contraception
Lactating, no contraception
Probability of pregnancy
Cumulative %
% women amenorrheic -▽-
Monthly % risk of pregnancy
Months postpartum
Months of lactational amenorrhoea
Post partum, lactating + post menstrual contraception
Short RV, Lewis PR, Renfree MB, Shaw G (1991) The contraceptive effects of extended periods of lactational amenorrhoea. The Lancet 337,

31. Lactational control of hormonal cycles:
Lactational control of reproduction:
Prolactin release important in suppressing cyclic release of gonadotrophins.
Endogenous opiates (beta endorphins) are also involved.
Frequency of suckling very important in lactational amenorrhoea

32. Summary nutrition, energy, water, immune protection for newborn
mammary gland has multiple lobules
alveoli  secretory epithelium
myoepithelial cells  OT & milk ejection
well vascularized
development induced by hormones – prolactin, Prog, E2 etc
placental lactogens in pregnancy
initially colostrum (immunoglobulins)  mature milk
oxytocin & Fergusson reflex + CNS
lactational control of reproductive cycles - role of endorphins
anoestrus
diapause