1. HORMONAL CONTROL OF MAMMOGENESIS, LACTOGENESIS, AND GALACTOPOIESIS

2. MAMMOGENESIS Growth hormone (anterior pituitary) Estrogen (ovary)
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. Produced in the ovary (placenta)
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 Growth hormone and prolactin-like activities
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

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. Prolactin - rodents GH - ruminants * MUST REMOVE MILK FROM GLAND*
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!!!

32. PROLACTIN
SECRETION

33. OXYTOCIN

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

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. EXTRA CREDIT # 2 QUESTION (10 PTS)
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!!!