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 partial 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