Womens Health Med Chem Flashcards
ER signaling
1) Bind to estrogen receptor
2) ER Transciption factor tether
3) growth factor phosphorylate ER
4) non genomic actions: cytoplasm proteins
Estrogen
Female maturation Endometrial effects Metabolic bone resorption Adipose leptin Blood coagulability 2,7,9,10
Tamoxifen
Raloxifene, clomiphene
Blocks ER
Selective estrogen receptor modulator
SERM-ifen, iphene
Partial agonist antagonist
For breast cancer
Major estrogens
Estriol, estrone, estradiol
Estradiol is major secretory product of the ovary
Precursor for estrogen synthesis
Pregnenolone -> androstenedione ->
Aromatase to produce estrone and estradiol
Estrone is precursor for estriol
Pulsatile GnRH
Endogenous
Fertility
GnRH agonist (less multiple gestations)
Clomiphene: competitive inhibitor of endogenous estrogen and blocks negative feedback, stimulate ovulation
DC clomiphene if visual AE
Contraception
Oral contraceptive: consistent high estrogen & progestin levels inhibit GnRH, inhibit FSH, LH (release and egg maturation), insufficient endometrial thickening, thick cervical mucus
Danazol: inhibits LH/FSH surge
Endometriosis
Ketoconazole
Danazol: suppress ovarian function and midcycle LH/FSH surge
Synthetic androgen
Androgens cause atrophy
Breast cancer
Fulvestrant - pure ER antagonist (if resistant to tamoxifen)
SERM
Anatrozole, letrozole Aromatase inhibitors (decrease estrogen production)
Exemestane: irreversible Aromatase inhibitor
Most breast cancer cells are ER+ and proliferate by estrogen
Block androgen conversion to estrogen
GnRH
Stimulates release of FSH/LH
FSH
Develops follicles, estrogen secretion, and induces expression of LH receptors
LH
Regulates Aromatase ( production of 17B-estradiol from testosterone)
Surge LH= ovulation
HPA negative feedback
Estrogen and progesterone on GnRH
Inhibin on FSH release
GnRH neurons
Stimulated by NE neurons
Inhibited by opioid, dopamine, GABA