lecture 18: lactation

Question 1

What is lactation?

Answer 1

• primary source of nutrition and energy for newborn mammal
• immune protection
• mammary glands change - hormones and development
• variation between species: e.g.
  
  • number of glands: human 2; wallaby 4; pig 18; cow 4 (apposed in single udder)
• in a way lactation is the thing that characterises mammals

Question 2

What is an example of variation in milk composition between species?

Answer 2

• human:
  
  • water = 90 g/100mL
  • protein = 1.1 g/100mL
  • carbohydrate = 7.5 g/100mL
  • lipid = 4.2 g/100mL
  • energy (MJ/L) - 3.3
• elephant seal:
  
  • water = 35
  • protein = 10
  • carbohydrate = 2
  • lipid = 55
  • energy = 23
• elephant seals require more energy from the mother in order to survive the cold
• the pups have to develop a thick layer of insulating blubber very quickly
• dramatic differences between species that relate to environmental constraints and all sorts of other things

Question 3

What is the structure of a mammary lobule?

Answer 3

• e.g. cluster of alveoli in the goat
  
  • capillaries
  • venule
  • arteriole
  • myoepithelial cells
  • alveolar epithelial cells
  • alveolus
  • milk
  • milk duct
• want to maximise surface area so there are a number of epithelial cells that can produce secretions → package into alveoli that are interconnected by milk ducts
• these cells are very metabolically active
  
  • some high yielding dairy cows might produce two udders worth of milk a day → a lot of milk
• fantastic vascular system
• capillary beds surrounding each of the alveoli
• huge amount of opportunity for exchange of nutrients between blood and epithelial cells
• milk ducts coalesce in different lobules → down towards teat

Question 4

What is the structure of mammary lobules and alveoli?

Answer 4

• note vascular supply around alveolus
• myoepithelial cells surrounding alveolus contract, increasing intra-mammary pressure at milk let-down
• not just alveoli and blood vessels
• connective tissue
• ducts
• adipose tissue → fat → most of human mammary tissue
• pregnant women → mammary glands get bigger but the amount of fat probably stays the same
• alveolus
  
  • secretory epithelial cells
  • surrounded by a cluster of cells called myoepithelial cells → flat, squamous sort of cells, muscle-like characteristics, respond to oxytocin
  • when you fill your alveolus with milk oxytocin causes contraction of myoepithelial cells → increases the intraalveolar pressure which squishes the milk out
  • highly specialised epithelium
  • basement membrane → gives structural support
  • specialised junctions between epithelial cells
  • milk is not just things from the blood oozing through leaky membrane

Question 5

What are duct systems in different species?

Answer 5

• rat
  
  • alveoli
  • lactiferous ducts
  • galactophore
  • nipple
• rabbit
  
  • galactophore → multiple milk ducts ending on the teat
  • nipple
• woman
  
  • lactiferious sinus
  • areola
  • nippe
  • 15 - 20 mammary lobes dilating as lactiferous sinus emerging at nipple
• ruminant
  
  • galactophores
  • gland cistern → can get a lot of milk out very quickly
  • teat cistern
  • teat canal

Question 6

How do mammary glands develop in the foetal mouse?

Answer 6

• normal female → development of gland, nipple etc
• ovariectomised female → mammary glands still differentiate therefore don’t need ovarian hormones to develop mammary gland
• normal male → remnant of mammary gland, epidermis shows no sign of nipple formation
• castrated male → development of mammary glands
• androgens cause regression of the mammry primordia

Question 7

What is postnatal mammary growth in rat?

Answer 7

• pre-pubertal
  
  • atrophic ducts and very little mammary development
  • oestrogen + growth hormone → adrenal steroids →
• pubertal
  
  • duct growth
  • oestrogen + progesterone + prolactin + growth hormone + adrenal steroids
• post-pubertal
  
  • lobulo-alveolar growth
  • cyclic changes through oestrous/menstrual cycles
  • prolactin + adrenal steroids →
• late-pregnancy → lactation
  
  • milk secretion
• oestrogen, progesterone, cortisol, growth hormone, placental lactogen and prolactin needed for mammary growth during first pregnancy

Question 8

What is the mammary gland cycle?

Answer 8

• virgin → pregnancy → lactation → involution → pregnancy etc
• duct structures in virgin female have little development
• pregnancy → development
• lactation → secretory etc
• involution → milk production shuts down after relatively shuts down

Question 9

Summary of structure and development of the mammary gland?

Answer 9

• structure of mammary gland – variations on a theme
  
  • ducts and cisterns (cisterns can offload a lot of milk in a short time, helpful when you feed infrequently)
  • 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
• foetal 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

Question 10

How does hormonal regulation of milk secretion differ between species?

Answer 10

• to maintain high milk production after removal of the pituitary gland:
  
  • rats need: prolactin, Adrenocorticotrophin (ACTH)
  • sheep and goats need: growth hormone, prolactin, ACTH, thyroptrophin
  • rabbits need: prolactin
• ACTH maintains cortisol secretion from the adrenal gland
• TSH maintains thyroid hormone secretion from the thyroid gland

Question 11

What is the hormonal control of milk secretion?

Answer 11

• 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)

Question 12

What is the composition of breast milk at diffrent time points?

Answer 12

• colostrum (onset of lactation)
  
  • high protein
  • rich in immunoglobulins
• mature milk
  
  • 7% lactose
  • 4% fat
  • 1% protein
  • • minerals, vitamins etc
• two 25 mL samples of human breast milk
  
  • foremilk: the watery milk coming from a full breast
  • hindmilk: the creamy milk coming from a nearly empty breast
• late pregnancy
  
  • high levels of progesterone, oestrogens
  • prolactin, hPL (hPL drops off dramatically at birth)
• milk secretion turns on after birth, maybe a small amount before
• prolactin stays high during lactation
• sensory stimuli through teats

Question 13

What are the hormones involved in pregnancy and peripartum in regards to lactation?

Answer 13

• 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

Question 14

What is local regulation of lactation?

Answer 14

• FIL - feedback inhibitor of lactation
• small protein secreted in alveolus
• if not removed by emptying alveolus, it acts to suppress further milk secretion

Question 15

What are mammary secretory processes?

Answer 15

• 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 and growth factors
• paracellular: immune cells; leakiness may be high in disease states increasing transfer of interstitial fluids

Question 16

What are the phases of lactation?

Answer 16

• milk secretion
  
  • initiation of milk secretion begins in pregnancy
  • prolactin and other hormones
  • synthesis of milk constituents within alveolar cells
  • intracellular transport of milk componenets
  • 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

Question 17

What is the importance of sucking?

Answer 17

• in milk secretion
• sucking induced release of prolactin
• prolactin
  
  • VIP = vasoactive intenstinal peptide
  • potent Prl releasing factor
• dopamine from TIDA nerves
  
  • DA is a Prl release inhibitory factor

Question 18

What is the milk ejection reflex?

Answer 18

• sucking-induced release of oxytocin
• hypothalamus-hypophyseal tract: increased firing rate after nipple or reproductive tract stimulation causes increased oxytocin secretion

Question 19

What is the effect of anticipation of milking on oxytocin concentrations in cows?

Answer 19

• PM: preparation for milking
• MA: application of teat cups
• S: stripping
• C: control level

Question 20

What regulates the response to milk ejection?

Answer 20

• oxytocin receptors

Question 21

What is the Hottentot method of inducing milk let down?

Answer 21

• Ferguson Reflex → oxytocin positive feedback in uterine contractions

Question 22

What is the hormonal control of lactation?

Answer 22

• 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

Question 23

How does milk composition changes?

Answer 23

• changes in peripartum period
• milk composition in women pre- and post-partum
• 0 indicates time of birth

Question 24

What are variances in milk composition?

Answer 24

• 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

Question 25

What is lactation in marsupials?

Answer 25

• milk composition changes in marsupials
• high in carbohydrates early
• middle levels of proteins and lipids
• ultimately high in lipids, v low in carbohydrates
• protein levels remain similar

Question 26

What is milk ejection in the agile wallaby?

Answer 26

• 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

Question 27

What is prolactin related suppression of reproductive cycle?

Answer 27

• 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)

Question 28

What are the contraceptive effects of breastfeeding?

Answer 28

• cumulative % probability of pregnacy
  
  • non-lactating, no contraception → relatively high even immediately post partum
  • lactating, no contraception
    
    • low initially, increases
  • post partum, lactating + post menstrual contraception
    
    • low with v moderate increase
• monthly % risk of pregnancy vs months of lactational amenorrhoea
  
  • increases with time
• contraceptive effects of extended periods of lactational amenorrhoea

Question 29

What is the lactational control of reproduction?

Answer 29

• prolactin release important in suppressing cyclic release of gonadotrophins
• endogenous opiates (beta endorphins) are also involved
• frequency of suckling very important in lactational amenorrhoea

Question 30

summary

Answer 30

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