lecture 18: lactation Flashcards
1
Q
What is lactation?
A
- 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
2
Q
What is an example of variation in milk composition between species?
A
- 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
3
Q
What is the structure of a mammary lobule?
A
- 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
4
Q
What is the structure of mammary lobules and alveoli?
A
- 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
5
Q
What are duct systems in different species?
A
- 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
6
Q
How do mammary glands develop in the foetal mouse?
A
- 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
7
Q
What is postnatal mammary growth in rat?
A
- 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
8
Q
What is the mammary gland cycle?
A
- 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
9
Q
Summary of structure and development of the mammary gland?
A
- 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
10
Q
How does hormonal regulation of milk secretion differ between species?
A
- 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
11
Q
What is the hormonal control of milk secretion?
A
- 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)
12
Q
What is the composition of breast milk at diffrent time points?
A
- 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
13
Q
What are the hormones involved in pregnancy and peripartum in regards to lactation?
A
- 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
14
Q
What is local regulation of lactation?
A
- FIL - feedback inhibitor of lactation
- small protein secreted in alveolus
- if not removed by emptying alveolus, it acts to suppress further milk secretion
15
Q
What are mammary secretory processes?
A
- 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
16
Q
What are the phases of lactation?
A
- 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
17
Q
What is the importance of sucking?
A
- 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
18
Q
What is the milk ejection reflex?
A
- sucking-induced release of oxytocin
- hypothalamus-hypophyseal tract: increased firing rate after nipple or reproductive tract stimulation causes increased oxytocin secretion
19
Q
What is the effect of anticipation of milking on oxytocin concentrations in cows?
A
- PM: preparation for milking
- MA: application of teat cups
- S: stripping
- C: control level
20
Q
What regulates the response to milk ejection?
A
- oxytocin receptors
21
Q
What is the Hottentot method of inducing milk let down?
A
- Ferguson Reflex → oxytocin positive feedback in uterine contractions
22
Q
What is the hormonal control of lactation?
A
- 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
23
Q
How does milk composition changes?
A
- changes in peripartum period
- milk composition in women pre- and post-partum
- 0 indicates time of birth
24
Q
What are variances in milk composition?
A
- 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
25
What is lactation in marsupials?
* 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
26
What is 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
27
What is prolactin related suppression of reproductive cycle?
* 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)
28
What are the contraceptive effects of breastfeeding?
* 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
29
What is the 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
30
summary
* 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
