Post on 14-Dec-2015
transcript
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
RodentDay 9
PREGNANCY
RodentDay 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 tocorticoid 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)
Afferent nervesInguinal Nerve
Spinal Cord
Hypothalamus
Anterior Pituitary
Prolactin
Alveoli secrete milk
Posterior Pituitary
Oxytocin & Neurophysin
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 Th 2/5 (Th before exam)• Can give to Sarah, Erin, Kevin or me in class or send
via email .• HAVE A FANTASTIC WEEKEND!!!