HORMONAL CONTROL OF MAMMOGENESIS, LACTOGENESIS, AND GALACTOPOIESIS

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HORMONAL CONTROL OF MAMMOGENESIS,
LACTOGENESIS, AND GALACTOPOIESIS
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MAMMOGENESIS

• MAMMOGENIC COMPLEX OF HORMONES
• Growth hormone (anterior pituitary)
• Estrogen (ovary)
• Progesterone (ovary)
• Prolactin ( anterior pituitary)
• Glucocorticoids (adrenal glands)
• Placental lactogen ( placenta)
• Local mammary factors (IGF, TGF, EGF)
• SPECIES DIFFERENCES!

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GROWTH HORMONE

• Produced in the anterior pituitary
• Been shown to influence mammary development even
  in the fetal stages
• Mammary parenchyma correlated to GH
• Receptors on epithelial / stromal tissue
• MOST EFFECTS MEDIATED THROUGH LOCAL STROMAL
  FACTORS (IGF)

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GLUCOCORTICOIDS (C)

• Produced in the adrenal glands
• Involved in nutrient metabolism
• Shown to be involved in both
• - ductal development with GH and E2
• - lobulo/alveolar growth GH, PRL, E2, P4
• DIRECT vs. INDIRECT EFFECTS?

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ESTROGEN (E2)

• Produced in the ovary (placenta)
• SPECIES SPECIFICITY!!!!!
• Parenchymal development even very early
• - rodents, bovine essential
• - sheep ovex and still get development
• Parenchymal development species specific
• - rodents duct / stroma bovine duct
• Mediated through local factors IGF

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Rodent
4 weeks old
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PUBERTY TO CONCEPTION
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PROGESTERONE (P4)

• Produced in the ovary ( placenta)
• Lobulo-alveolar devLactogenesis-stage 1
• Function of high E2 and P4 ( GH, PL, C)
• - luteal phase some dev./ milk synthesis?
• - pregnancy massive development P4/E2
• especially late pregnancy
• Inhibitory to lactogenesis (Stage 2)?

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PUBERTY TO CONCEPTION
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PREGNANCY
Rodent Day 9
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PREGNANCY
Rodent Day 16
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PROLACTIN

• Produced in the anterior pituitary
• SPECIES SPECIFIC!!
• Bovine Permissive effect for steroids
• Rodents ESSENTIAL for mammo.
• Regression of elongated terminal end buds
• Promotes ductular side branches
• Direct effect on lobulo- alveolar development

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Rodent
4 weeks old
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PLACENTAL LACTOGEN

• Produced by the placenta (fetal origin
• Growth hormone and prolactin-like activities
• Linkage to calf size / future milk production?
• Mediated by local factors (IGF)?

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MAMMOGENIC HORMONE ACTIONS

• Related to hormone concentrations
• Related to tissue sensitivity
• - increase in receptors / late pregnancy
• Hormone biological availability
• - Steroid hormones bound to transport proteins
  glucocorticoids

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LOCAL TISSUE MEDIATORS

• Growth factors
• Transforming growth factors (TGF)
• - down regulate development
• Epidermal growth factors (EGF)?
• Fibroblast growth factors (FGF)?
• Insulin-like growth factors (IGF)!!!

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INSULIN-LIKE GROWTH FACTORS

• Widely expressed peptides
• - cell growth - cell differentiation
• - maintenance of cell function
• - Prevention of apoptosis
• Without IGF, E2 and GH dont develop mammary
  gland!!
• Mediated through IGF binding proteins
• prolong life transport localize

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INSULIN-LIKE GROWTH FACTORS
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PARTURITION - LACTOGENESIS
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PARTURITION - LACTOGENESIS

• Lactogenic complex of hormones
• - Insulin / IGF?
• Glucocorticoids
• Prolactin
• - estrogen
• - growth hormone
• thyroid hormones

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PARTURITION - LACTOGENESIS
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PARTURITION - LACTOGENESIS
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PARTURITION - LACTOGENESIS
P4
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PARTURITION - LACTOGENESIS

• Insulin / IGF 1
• - cell division
• - carbohydrate metabolism
• Growth hormone / IGF?
• - nutrient uptake
• - mammary blood flow
• Thyroid hormones
• - increased metabolism

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PARTURITION - LACTOGENESIS

• GLUCOCORTICOIDS
• development of RER
• casein
• ? - lactalbumin
• P4 drop decreases binding to
• corticoid binding globulin
• PROGESTERONE
• - Can get milk w/ out

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PARTURITION - LACTOGENESIS

• PROLACTIN
• - casein / ? - lactalbumin transcription
• - milk protein mRNA translation
• - fatty acid synthesis
• - swelling of golgi apparatus
• - lactose synthesis

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PARTURITION - LACTOGENESIS
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ARTIFICIAL INDUCTION OF LACTATION

• WHAT HORMONES
• ARE
• INVOLVED?

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ARTIFICIAL INDUCTION OF LACTATION

• Estrogen .1 mg/kg/day in oil 2X/12 hr.
• Progesterone .25 mg/kg/day
• E2 and P4 given for 7 days ( days 1-7)
• Dexamethasone 20 mg/d (day 18, 19-20?)
• Milk on day 21 or when engorged w/milk
• Reserpine tranquilizer that prolactin
• (days 8, 10, 12, 14)

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GALACTOPOIESIS

• Prolactin!
• Growth hormone!
• Glucocorticoids
• Thyroid hormones
• SPECIES SPECIFIC!
• Prolactin - rodents GH - ruminants
• IGF!
• MUST REMOVE MILK FROM GLAND

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Milk Letdown

• Stimulus

Hypothalamus
Afferent nerves
Inguinal Nerve
Anterior Pituitary
Posterior Pituitary
Spinal Cord
Oxytocin Neurophysin
Prolactin
Alveoli secrete milk
Alveoli contract
MmmmMILK!!!
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PROLACTIN
SECRETION
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OXYTOCIN
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What prevents milk letdown?

• STRESS!!!
• Sympathetic innervation vasoconstriction
• Central Inhibition
• Failure of oxytocin to be released
• Peripheral Inhibition
• Failure of oxytocin to reach myoepithelial cells
• - Failure of oxytocin receptors
• Oxytocin-short 1/2 life
• 5 minutes

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Constriction of blood vessels