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HORMONAL CONTROL OF MAMMOGENESIS, LACTOGENESIS, AND GALACTOPOIESIS

HORMONAL CONTROL OF MAMMOGENESIS, LACTOGENESIS, AND GALACTOPOIESIS. MAMMOGENESIS. MAMMOGENIC COMPLEX OF HORMONES Growth hormone (anterior pituitary) Estrogen (ovary) Progesterone (ovary) Prolactin ( anterior pituitary) Glucocorticoids (adrenal glands) Placental lactogen ( placenta)

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HORMONAL CONTROL OF MAMMOGENESIS, LACTOGENESIS, AND GALACTOPOIESIS

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  1. HORMONAL CONTROL OF MAMMOGENESIS, LACTOGENESIS, AND GALACTOPOIESIS

  2. 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!

  3. 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)

  4. 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?

  5. 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

  6. Rodent 4 weeks old

  7. PUBERTY TO CONCEPTION

  8. PROGESTERONE (P4) • Produced in the ovary ( placenta) • Lobulo-alveolar dev:Lactogenesis-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)?

  9. PUBERTY TO CONCEPTION

  10. PREGNANCY Rodent Day 9

  11. PREGNANCY Rodent Day 16

  12. 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

  13. Rodent 4 weeks old

  14. 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)?

  15. 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

  16. 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)!!!

  17. INSULIN-LIKE GROWTH FACTORS • Widely expressed peptides - cell growth - cell differentiation - maintenance of cell function - Prevention of apoptosis • Without IGF, E2 and GH don’t develop mammary gland!! • Mediated through IGF binding proteins * prolong life * transport * localize

  18. INSULIN-LIKE GROWTH FACTORS

  19. PARTURITION - LACTOGENESIS

  20. PARTURITION - LACTOGENESIS • Lactogenic complex of hormones • - Insulin / IGF? • ** Glucocorticoids • ** Prolactin • - estrogen • - growth hormone • thyroid hormones

  21. PARTURITION - LACTOGENESIS

  22. PARTURITION - LACTOGENESIS

  23. PARTURITION - LACTOGENESIS P4

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

  25. PARTURITION - LACTOGENESIS • GLUCOCORTICOIDS • * development of RER • * casein • *  - lactalbumin • *P4 drop decreases binding to • corticoid binding globulin • PROGESTERONE • - Can get milk w/ out

  26. PARTURITION - LACTOGENESIS • PROLACTIN - casein /  - lactalbumin transcription - milk protein mRNA translation - fatty acid synthesis - swelling of golgi apparatus - lactose synthesis

  27. PARTURITION - LACTOGENESIS

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

  29. Milk Letdown Stimulus (pleasurable) Hypothalamus Afferent nerves Inguinal Nerve Anterior Pituitary Posterior Pituitary Spinal Cord Oxytocin & Neurophysin Prolactin Alveoli secrete milk Alveoli contract Mmmm…MILK!!!

  30. PROLACTIN SECRETION

  31. OXYTOCIN

  32. 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

  33. Constriction of blood vessels

  34. ARTIFICIAL INDUCTION OF LACTATION WHAT HORMONES ARE INVOLVED?

  35. 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)

  36. AS 337 LACTATION BIOLOGY EXTRA CREDIT # 2 QUESTION (10 PTS) • How can lactation be induced (how was Tom Cruise going to nurse his baby or an animal who is not pregnant initiate a new lactation)? Look for strategies, products, organizations, or interesting information about induction of lactation in any species and/or male lactation. Share what you find and where you found it. • DUE ON/ BEFORE CLASS Th2/6 (Th before exam) • Can give to Melissa, Kali, Mackenzie, Brittany or me in class or send via email . • HAVE A FANTASTIC WEEKEND!!!

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