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BIOL30001 Reproductive Physiology
Lactation: The final phase of mammalian reproduction
Geoff Shaw
EssRep7 Chapter 18J&E6: Chapter 14.Hormonal control of lactation, A.Cowie in Hormonal Control of Reproduction:
Austin & Short. Book 3, Chapter 8:
Physiology of Reproduction 1994 4th 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: 583-590
Margaret C. Neville. (1998) Milk Secretion: an overview. http://mammary.nih.gov/reviews/lactation/Neville001/index.html
References
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)
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
From Austin and Short 1984
Structure of a mammary lobuleeg. cluster of alveoli in the goat
milk
Alveolus
alveolar epithelial cells
myoepithelial cells
capillaries
milk duct
venule
arteriole
J and E, Fig 14.3
Note vascular supply aroundalveolus
myoepithelialcells surroundingalveolus contract, increasing intra-mammary pressure at milk let-down
Structure of mammary lobules and alveoli
J and E Fig14.2
15-20 mammary lobesDilating as a lactiferous sinus emerging at nipple
duct systems in different species
Ovariectomisedfemale
Castrated maleNormal male
Normal female
From Austin and Short 1984
Development of mammary gland in fetal mouse
androgens cause regression of the mammary primordia
From Austin and Short 1984
Oestrogen, progesterone, cortisol, growth hormone, placental lactogen and prolactin needed for mammary growth during first pregnancy
Postnatal mammary growth in ratpre-pubertal
pubertal
post-pubertal
late-pregnancy lactation
cyclic changes through oestrous / menstrual cycles
Mammary gland cycle
http://mammary.nih.gov/atlas/wholemounts/normal/index.html
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
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
ACTH maintains cortisol secretion from the adrenal gland
† TSH maintains thyroid hormone secretion from the thyroid gland
Milk secretion requires hormonal support but species’ needs vary
Hormonal regulation of milk secretion differs between species
Mammary gland transplanted to the neck of a goat (Jim Linzell’s experiment)- separated from nerve supply- continued milk secretion
However milk removal necessary for continued lactation(Malcolm Peaker)
Control is hormonal, not neural
Milk secretion: hormonal control
J & E 14.5
Onset of lactation in women
Pregnancy, hormones and milk secretion
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
http://en.wikipedia.org/wiki/Human_milk
• 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
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.
Mammary secretory processes
I. exocytosis: proteins made via RER and Golgi; Lactose
II. apocrine secretion of lipids; vesicle membranes phospholipids
III. trans-membrane: water; small molecules; drugs
IV. trans-cytosis: immunoglobulins; some hormones & growth factors
V. paracellular: immune cells; leakiness may be high in disease states increasing transfer of interstitial fluids.
http://mammary.nih.gov/reviews/lactation/Neville001/index.html
Milk Fat Globule
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
ProlactinVIP = Vasoactive intestinal peptide , - VIP a potent Prl releasing factor
Dopamine from TIDA nerves, - DA a Prl release inhibitory factor
EssRep7 18.6
Sucking induced release of prolactin.
Milk secretion: The importance of sucking
EssRep7: 18.7
Sucking-inducedrelease of oxytocin.
The milk ejection reflex
PM preparation for milking; MA application of teat cups; S stripping; C control level.From Austin and Short 1984
Milk ejection: Anticipation of milking on oxytocin concentrations in dairy cows
Hottentot method of inducing milk let down (Ferguson Reflex)
Milk ejection: the role of oxytocin
Oxytocin receptors during pregnancy and lactation in rat mammary gland from Soloff and Weider 1983
Milk ejection: Oxytocin receptors regulate response
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.
Milk compositionin women pre- and post-partum.
0 indicates time of birth
From Kulski and Hartmann,1981
Milk composition: Changes in peripartum periodcolostrum
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
Milk composition changes in marsupialsFrom Green 1984
Lipids
Proteins
Carbohydrates
Lactation in marsupials
from Lincoln and Renfree 1981
difference in response to OT allows milk ejection in gland with PY continuously attached
sucking by young at foot causes ME in both glands
Milk ejection in the agile wallaby -concurrent asynchronous lactation
intr
a-m
amm
ary
pre
ssur
e
• 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)
Prolactin related suppression of reproductive cyclesuckingstimulus
nipple
spinal cord
hypothalamus
β-endorphin release
milkejection
oxytocin
lactationalinfertility
GnRH pulse generator
milk production
prolactin
dopamine release
- -
-
Non lactating, no contraception
Lactating, no contraception
Post partum, lactating + post menstrual contraception
Contraceptive effects of breastfeeding
Short RV, Lewis PR, Renfree MB, Shaw G (1991) The contraceptive effects of extended periods of lactational amenorrhoea. The Lancet 337, 715-717.
Cu
mu
lativ
e %
P
roba
bili
ty o
f pre
gn
ancy
Mo
nth
ly %
ris
k o
f pre
gna
ncy
Months postpartum Months of lactational amenorrhoea
% w
omen
am
eno
rrh
eic
-▽-
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
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