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7-Biology of Lactation > Slide Set 4: Lactogenesis > Flashcards

Slide Set 4: Lactogenesis Flashcards

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1
Q

Define Lactogenesis

A

Ø A series of cellular changes whereby mammary epithelial cells are converted from a non-secretory state to a secretory state.
Ø There is an increase in RNA:DNA ratio (from 1:1 during pregnancy to 2:1 in early lactogenesis)

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2
Q

Lactogenesis consists of two stages:

A

Stage I:
Cytologic & enzymatic differentiation of the epithelial cell

Stage II:
Copious secretion of milk

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3
Q

When does stage 1 of lactogenesis happen?

A
  • Occurs before parturition (prepartum)

- In cows (9 mon.) 4 month, goats (5 mon), 3 month, rats (3 weeks) 30 h prepartum, women (9 mon) mid. pregnancy

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4
Q

What occurs during lactogenesis stage 1?

A
  • Coincides with colostrun formation and immunoglobulin uptake
  • Limited milk synthesis and secretion
  • No lactose biosynthesis
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5
Q

Example of enzymatic differentiation in stage 1:

A

Ø Increased synthesis of enzymes necessary for synthesis of milk components

Ø Increased # of transport systems for milk precursors (e.g. amino acids & glucose)

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6
Q

What are some histological changes that occur in lactogenesis stage 1:

A

Ø Prominent rough endoplasmic reticulum
Ø Marked increase in the # of mitochondria
Ø Prominent Golgi bodies
Ø Lipid and protein granules accumulate in the lumen
Ø Increase in the size of the alveoli
Ø Closure of tight junctions

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7
Q

What happens during lactogenesis stage 2?

A

Copious secretion of milk:

Significant increase in mammary blood flow and substrate uptake

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8
Q

In cows, stage 2 of lactogenesis begins _____ and humans _____
pigs & mice _____

A

0-4 pre-partum and lasts for few days post-partum
2-3 post-partum
at parturition

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9
Q

What initiates lactogenesis stage 2

A

The pre-partum removal of secretion could initiate lactogenesis II

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10
Q

What are the changes in mammary secretion during lactogenesis?

A 
Lactogenesis I (colostrogenesis)
High concentrations of protein, immunoglobulins, Na, Cl Low concentrations of lactose, K, citrate

Lactogenesis II
High concentrations of lactose and K Low concentrations of protein, fat

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11
Q

What are lactogenic hormones?

A
  • Prolactin
  • ACTH (glucocorticoids)
  • Estrogen
  • Absence of progesterone
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12
Q

In most mammals, birth and ______coincide with the withdrawal of progesterone

A

lactogenesis II

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13
Q

When does the progesterone drop occur in humans?

A

In humans, the major fall in progesterone occurs after birth (30-40 h after birth)

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14
Q

How is lactogenesis 2 and human baby body weight related?

A

Human infants have significant fat reserves and slow rate of neonatal growth

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15
Q

How long does the lactogenesis 1 last for?

A

mid pregnancy to day 2 postpartum

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16
Q

What happens during lactogenesis 1 in hormonal and tissue level in humans

A
  • Differentiation of secretory cells
  • Prolactin stimulates mammary epithelial secretory cells
  • Progesterone inhibits prolactin secretory activities during late pregnancy
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17
Q

What happens during lactogenesis 1 in hormonal and tissue level in humans?

A
  • Differentiation of secretory cells
  • Prolactin stimulates mammary epithelial secretory cells
  • Progesterone inhibits prolactin secretory activities during late pregnancy
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18
Q

When does colostrum start forming in humans?

A

Mother will start making colostrum half way through pregnancy (endocrine control system)

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19
Q

When does lactogenesis 2 occur?

A

day 2 to day 5 pospartum

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20
Q

What happens during lactogenesis 2 in hormonal and tissue level in humans?

A
  • The delivery of placenta results in sudden drop progesterone levels
  • Triggered by rapid drop in mother’s progesterone and high prolactin levels
  • Closure of tight junctions in alveolar cells
  • Switch from endocrine to autocrine (local) control
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21
Q

What are the hormones involved in lactogenesis 2?

A

Major hormones: prolactin & glucocorticoids

Other hormones: growth hormones, insulin & thyroxin

22
Q

Compare baby pigs and human babies in terms of birth weight and lactation

A 
Pigs
Ø Born with little body fat 
Ø Double its birth wt in the 1st
week of life
Ø Consumes 50-100 ml colostrum within 4 h after birth

Human
Ø Born with significant body fat
Ø May regain birth wt after the 1st week
Ø Consumes 30-40 ml of colostrum during the first 24 h of life
Ø Increase to 500-750 ml/d of milk, 5 days post-partum

23
Q

How do prolactin and oxytocin control milk secretion/ejection

A
  • Impulses arising in sensory terminals of the nipples (suckling) follow common pathways
  • They activate different nuclei in the
    hypothalamus
24
Q

Why can be there a delay in lactation?

A
  • Not all women experience lactogenesis phase II 3-4 post-partum
  • Possible reasons: cesarean birth, obesity, placental retention, stress.
25
Q

How can lactation be inhibited?

A
  • Lactogenesis does not begin in humans until the rapid decrease in estrogen and progesterone 2-3 d post-partum
  • Exogenous steroids (combination of estrogen & progesterone) can be used to maintain high circulating levels after or/at delivery
  • Both hormones inhibit glucorticoid receptors (inhibit RER formation and protein synthesis)
  • Bromocriptine can be used as a medical therapy for milk inhibition
  • Highly effective in lowering prolactin concentration post-partum
  • Cabergoline (prolactin lowering medication) can be given within 24-h after delivery
  • Both medications are no longer recommended (major adverse reactions)
  • Supportive measures can be effective: (use of breast binders, tight brassiere, use of ice pack, avoidance of coffee, tea and nipple stimulation)
26
Q

What are the names of the 2 drugs that can be taken to inhibit lactation or treat hyperprolactinemia?

A
  • Bromocriptine can be used as a medical therapy for milk inhibition
  • Highly effective in lowering prolactin concentration post-partum
  • Cabergoline (prolactin lowering medication) can be given within 24-h after delivery
27
Q

What are the mechanical ways of inhibiting lactation?

A

use of breast binders, tight brassiere, use of ice pack, avoidance of coffee, tea and nipple stimulation

28
Q

Where is prolactin secreted from?

A

Secreted by the anterior pituitary gland

29
Q

What is the role of prolactin in lactogenesis and what is its mechanism of action?

A

Ø A lactogenic hormone
Ø Binds to prolactin receptors on the mammary epithelial cell
Ø Increases milk protein synthesis
Ø Controls expression of genes necessary for casein
synthesis
Ø Involves in the maturation of Golgi body and appearance of secretory vesicles

30
Q

What are the roles of glucocorticoids in lactogenesis?

A

Ø Glucocorticoids (adrenal steroids) are lactogenic
Ø Glucocorticoids induce differentiation of rough
endoplasmic reticulum and tight junctions
Ø The differentiation is necessary for prolactin- induced protein synthesis
Ø Synergism between prolactin & glucocorticoids for lactogenesis

31
Q

What are the roles of estrogen in lactogenesis?

A

Ø Lactogenic (indirect effect)
Ø Increase secretion of prolactin and other
lactogenic hormones from pituitary gland
Ø Increases in the # of prolactin receptors in the mammary gland
Ø Stimulate synthesis of casein and a-lactalbumin
Ø Synergetic lactogenic effect with prolactin, glucocorticoids and estrogen

32
Q

What are the roles of progesterone in lactogenesis?

A

Ø Progesterone is anti-lactogenic

33
Q

What are the roles of progesterone in lactogenesis?

A

Ø Progesterone is anti-lactogenic

34
Q

TRUE/FALSE

Prolactin is anti-lactogenic in all mammals

A

FALSE

Progesterone is not anti-lactogenic in marsupials

35
Q

What are some other lactogenic hormones that are indirectly involved in lactogenesis?

A
  • placental lactogen
  • prostaglandin
  • insulin
  • growth hormone
36
Q

What are the roles of placental lactogen in lactogenesis?

A

Found in many (e.g. rats & mice) but not all mammalian species (e.g. rabbits)
Binds to prolactin receptors

37
Q

What are the roles of prostaglandin in lactogenesis?

A
  • Fatty acids produced by several tissues
  • Luteolytic enzyme (lyses corpus luteum and reduces secretion of progesterone)
  • Administration during pregnancy lead to abortion and lactogenesis
38
Q

What are the roles of insulin and growth hormone in lactogenesis?

A

Ø Insulin & insulin-like growth factor (IGF) may be involved in glucose uptake by the mammary gland (precursor of lactose)
Ø Growth hormone increases the secretion of IGF

39
Q

What is prolactin’s mechanism of action?

A

prolactin is a peptide hormone which means it cannot enter the epithelial cell

the binding will trigger a secondary messenger
cyclic amp CAMP
this will synthesize an enzyme called protein kinase. the function of this enzyme is the phosphorylation fo the amino acids - activating protein synthesis

the CAMP will also enter the nucleus of the epithelial cell to synthesize messenger RNA
- differentiation of the organelles

progesterone will inhibit the phosphorylation

40
Q

How does accumulation of milk in the mammary gland act on the hormonal pathways?

A

accumulation of milk will inhibit lactogenesis 2
this is an example of what happens to the dairy cow
the second activity will stimulate the brain and initiate the prolactin synthesis by inhibiting dopamine synthesis
accumulation of milk will inhibit milk production there is an antilactogenic component found in the dairy cows thats called dihydroxyketoprostaglandinF (DHKPGF)
prostaglandin is synthesized in the mammary gland that inhibits milk production
DHKPGF is inactive and this will be activated by PGF
the removal of both components will activate the milk secretion but the most important thing is the milk removal

41
Q

What does DHKPGF stand for? What is its function?

A

dihydroxyketoprostaglandinF

antilactogenic component found in the dairy cows
prostaglandin is synthesized in the mammary gland that inhibits milk production
DHKPGF is inactive and this will be activated by PGF
the removal of both components will activate the milk secretion but the most important thing is the milk removal

42
Q

What is the role of lactose in lactogenesis?

A

Ø There is little synthesis of a-lactalbumin during stage I of lactogenesis.
Ø High concentrations of prolactin, glucocorticoids & low concentration of progesterone initiates synthesis of a- lactalbumin.
Ø a-lactalbumin important for lactose synthesis (very important for milk production)

43
Q

TRUE/FALSE

Only the mammary gland can synthesize alpha lactalbumin

A

TRUE

This is the reason why lactose is only found in milk

44
Q

How is milk protein synthesis controlled?

A

prolactin and glucocorticoids will synthesize 2 milk prtoeins: casein and other whey rpotein

in golgi the lactose will be synthesized by lactose synethase and that will draw water inside the golgi body

lactose is the main osmole of the milk
high concentration of lactose inside the mamma gland will draw water

the more lactose = the more water in the milk and that deteremines the quality of the milk
high volume and more milk

it is extremenly impo to sytnehsize alpha lactalbumin

determeines the volume of milk

animals that have very little amuont of milk haee very low lactose

45
Q

What is the main osmole of milk?

A

lactose

high concentration of lactose will draw water inside the mammary gland

46
Q

What molecule is extremely important in synthesizing lactose

A

alpha lactalbumin

47
Q

What are the effects of hypophysectomy & hormonal administration on milk yield of goats?

A

the role of Thyroid Gland

they are synthesize inside the pit gland so if you remove it by hypophysectomy

  • this will immediately inhibit lactation
  • inject animals with glucocorticoids the milk production was not disrupted
  • bovine growth hormones were added but it didn’t restore completely
48
Q

What are the enzyme changes in lactogenesis?

A

For many mammals, removal of progesterone is a prerequisite for lactogenic enzyme activities
Ø The significant increase in lactogenic enzymes occurs at 1- parturition or 2- after parturition
Ø Example for group 1 is lactose synthetase
Ø Examples for group 2 are enzymes associated with
fatty acid synthesis (e.g. acetyl CoA carboxylase)
Ø Milk removal might be necessary for activities of other enzymes involved in lactogenesis

49
Q

What is a group 1 enzyme and what is its function?

A

lactose synthetase synthesizes lactose

50
Q

What is a group 2 enzyme and what is its function?

A

fatty acid synthesis (e.g. acetyl CoA carboxylase) synthesizes the fat components of milk

51
Q

How can you induce lactogenesis in non-pregnant women?

A

ØTwo phases
1- Stimulation of mamogenesis by injecting high levels of estrogen & progesterone
2-1 Injection of prolactin
2-2 Injection of glucocorticoids
~ 3 weeks of treatments
Ø Not effective for all cows
Ø Milk yield is lower than from cows giving birth

7-Biology of Lactation (16 decks)

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