HORMONAL CONTROL
OF MAMMOGENESIS,
LACTOGENESIS, AND
GALACTOPOIESIS
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
*  - lactalbumin
*P4 drop decreases binding to
corticoid binding globulin
• PROGESTERONE
- Can get milk w/ out
PARTURITION - LACTOGENESIS
• PROLACTIN
- casein /  - lactalbumin transcription
- milk protein mRNA translation
- fatty acid synthesis
- swelling of golgi apparatus
- lactose synthesis
PARTURITION - LACTOGENESIS
GALACTOPOIESIS
• Prolactin!
• Growth hormone!
• Glucocorticoids
• Thyroid hormones
• SPECIES SPECIFIC!
Prolactin - rodents GH - ruminants
• IGF!
* MUST REMOVE MILK FROM GLAND*
Milk Letdown
Stimulus (pleasurable)
Hypothalamus
Afferent nerves
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: 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
Constriction of blood vessels
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)
• 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 Tu 2/9 (exam day)
• Can give to Emily, Logan, Aislinn or me in class or
send via email .
• HAVE A FANTASTIC WEEKEND!!!