HORMONAL CONTROL OF MAMMOGENESIS, LACTOGENESIS AND GALACTOPOIESIS

Dr. DHIREN B. BHOI M.V.Sc., (Gynaecology) E. Mail:-drdhirenvet@gmail.com

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!

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)

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?

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

Rodent

4 weeks old

PUBERTY TO CONCEPTION

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)?

PUBERTY TO CONCEPTION

PREGNANCY

Rodent Day 9

PREGNANCY

Rodent Day 16

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

Rodent

4 weeks old

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)?

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

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)!!!

• • • •

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

INSULIN-LIKE GROWTH FACTORS

PARTURITION - LACTOGENESIS

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

PARTURITION - LACTOGENESIS

PARTURITION - LACTOGENESIS

PARTURITION - LACTOGENESIS

P4

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

PARTURITION - LACTOGENESIS
• GLUCOCORTICOIDS * development of RER * casein * α - lactalbumin *P4 drop decreases binding to corticoid binding globulin

• PROGESTERONE
- Can get milk w/ out

PARTURITION - LACTOGENESIS

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

PARTURITION - LACTOGENESIS

ARTIFICIAL INDUCTION OF LACTATION

WHAT HORMONES ARE INVOLVED?

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)

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

Milk Letdown
Stimulus Afferent nerves Inguinal Nerve Spinal Cord Prolactin Hypothalamus Anterior Pituitary Posterior Pituitary Oxytocin & Neurophysin Alveoli contract

Alveoli secrete milk

Mmmm…MILK!!!

PROLACTIN SECRETION

OXYTOCIN

What prevents milk letdown? STRESS!!!
• Sympathetic innervation • Central Inhibition
– Failure of oxytocin to be released

• Peripheral Inhibition
– Failure of oxytocin to reach myoepithelial cells

• Oxytocin-short 1/2 life
– ~5 minutes

• Women have less ...

Constriction of blood vessels

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