Vous êtes sur la page 1sur 38

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 Hypothalamus


Inguinal Nerve
Anterior Pituitary Posterior Pituitary
Spinal Cord
Prolactin Oxytocin &
Neurophysin
Alveoli secrete milk
Alveoli contract
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