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HORMONAL CONTROL OF MAMMOGENESIS, LACTOGENESIS, AND GALACTOPOIESIS.

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Presentation on theme: "HORMONAL CONTROL OF MAMMOGENESIS, LACTOGENESIS, AND GALACTOPOIESIS."— Presentation transcript:

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

21 PARTURITION - LACTOGENESIS

22

23 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) Afferent nerves Inguinal Nerve Spinal Cord Hypothalamus Anterior Pituitary Prolactin Alveoli secrete milk Posterior Pituitary Oxytocin & Neurophysin Alveoli contract Mmmm…MILK!!!

30

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32 PROLACTIN SECRETION

33 OXYTOCIN

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35

36 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

37 Constriction of blood vessels

38

39 ARTIFICIAL INDUCTION OF LACTATION WHAT HORMONES ARE INVOLVED?

40 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)

41 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 Th 2/5 (Th before exam) Can give to Sarah, Erin, Kevin or me in class or send via . HAVE A FANTASTIC WEEKEND!!!


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