Pharmacological control of mammogenesis, Lactogenesis and Galactopoiesis

Mohanad AlBayati
Mohanad AbdulSattar Ali Al-Bayati, BVM&S, MS, PhD Assistant Professor of Pharmacology and Toxicology Department of Physiology and Pharmacology College of Veterinary Medicine University of Baghdad Al Ameria, Baghdad Phone: 0964 7802120391 E. Mail: aumnmumu@covm.uobaghdad.edu.iq aumnmumu@yahoo.com

Growth hormone
Influence mammary gland development in fetal stage Development of parenchyma Up regulated their receptor in stromal and epithelial tissues Mediated their effect by Local Stromal Factor IGF

Glucocorticoids
Ductal development with GH andE2 Lobulo-alovular growth with GH,PRL,E2 and P4

Estrogen E2
Parenchymal development Rodent dectul-stroma development Bovine ductal development Mediated IGF

Progesterone P4
Lobulo-alovulo development E2-P4 leuteal phase patial development and milk synthesis and in pregnancy massive development (late pregnancy) Inhibitory of lactogenesis

Prolactine
Permissive effect of steroid in bovine Essential for mammogenic: - Regressive of elongated terminal end bud - Promote of ductular side branches - Lobulo-alovular development directly

Lactogen
Fetal placental origin GH and PL Like activity Future of milk production Mediated local factors GIF

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 and localize

PARTURITION - LACTOGENESIS
Lactogenic complex of hormones - Insulin / IGF Glucocorticoids Prolactin - estrogen - growth hormone thyroid hormones Relaxin Somtomedine

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

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

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

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 and 14)

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

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 Androgens Vasoconstrictors agents

Drugs mammogenic effects

Methylxanthines: caffeine and theophylline enhance mammotrophic hormone-induced mammary lobulo-alveolar differentiation c.AMP stimulant Nitric oxide donors