Flashcards in Female Sex Hormones Deck (61):
3 naturally occurring steroidal estrogens
estrone, estradiol, estriol
Nonsteroidal estrogenic compound
_____ is the major product of ovarian steroidgenesis
During first part of menstrual cycle estrogens are produced by theca and granulosa cell of _____
After ovulation, estrogens are produced by the ____
During pregnancy estrogens are produced by the ____
During menopause, estrogens are produced by ____
adrenal and hepatic conversion of precursors
____ and _____ are formed in the liver from estradiol or in peripheral tissues from andostendione.
Estrone/E1 and Estriol/E3
4 main female sex hormones
Progesterone, E1 estrone, E2 estradiol, E3 estriol
Product from which all sex hormones are derived is ____
pregnenolone (from cholesterol)
Two main male sex hormones
androstenedione and testosterone
_____ converts male sex hormones to estrogens.
Functions of estrogen
female maturation, endometrial proliferation during follicular phase, hematologic effect, metabolic effect
T/F estrogen is an important modulator of bone growth and fusion of ephiphyses
Hematologic effects of estrogens
increases coagulability of blood in extrinsic pathway (increased II, VII, IX, X and decreases antithrombin III) + increase in HDL, increased TAG --> unclear what the net effect is
Metabolic effects of estrogens
increased production of leptin, tbg, fibrinogen, transferrin, cbg, shbg
Estrogen is a vasodilator/vasoconstrictor
How does estrogen decrease resorption of bone?
promotes apoptosis of osteoclasts
In a non pregnant state, progesterone is produced by____
LH stimulated corpus luteum
In a pregnant state, progesterone is produced by the ____
Functions of progesterone
progestational profile of the endometrium/preparation for implantation, renders uterus refractory to oxytocin until onset of labor
4 types of steroid receptor ligands
pure agonist, mixed agonist/antagonist, pure antagonist I, pure antagonist II
MOA of pure agonist
agonist binds to receptor --> complex binds to HRE --> recruits coactivator -->gene transcription
MOA of mixed agonist/antagonist
Ligand binds to receptor --> complex binds HRE --> differential recruitment of co-activator/repressor --> abrogated gene transcription (type III-IV antagonist)
MOA of pure agonist II
ligand binds to receptor --> complex binds to HRE --> recruits co-repressor --> 0 gene transcription
MOA of pure agonist I
ligand binds to receptor --> complex does not bind HRE --> no gene transcription
T/F estrogen can have a genomic or a non-genomic resposne
T --> i.e. binding to blood vessels will vasodilate without a genomic response
How do natural and synthetic estrogens/progestins affect the pathway?
How does antiprogesterone RU486/mifepristone affect the pathway?
How does a selective ER modulator affect the pathway?
How do aromatase inhibitors affect the pathway?
3 indications of estrogen agonism
primary hypogonadism/secondary estrogen deficiency, suppression of ovulation, post-menopausal estrogen replacement
ERT increases/decreases HDL, increases/decreases LDL and increases/decreases oxidation of HDL/LDL.
increases, decreases, decreases
ERT increases/decreases the thickness of externa and media layers of the carotid but speeds up/delays intimal thickening.
ERT increases/decreases formation of angiotensin II.
ERT promotes/reverses acetylcholine induced vasoconstriction of the carotid.
T/F ERT relieves hot flashes, night sweats, vaginal dryness, and vaginal atrophy.
T/F ERT increases bone loss and hip fractures.
F --> reduces
T/F ERT increases colon cancer risk.
F --> reduces
T/F ERT decreases thrombotic risk.
F --> increases
T/F ERT increases stroke of risk.
T/F ERT increases incidence of ovarian/endometrial cancer.
T/F ERT decreases risk of breast cancer.
F --> increases
T/F ERT increases risk of MI.
MOA of SERMs
bind to ER --> complex binds to ERE in nucleus- -> conformational state dependent recruitment of coactivator/repressor --> tissue specific agonism/antagonism
Goal of SERM use
maintain good effects of ERT on bone, eliminate bad effects on endometrium and breast
suppresses E2 dependent growth of breast cancer (antagonist); agonist in uterus, bone
Tamoxifen is a type ___ estrogen receptor modulator
Tamoxifen is tumoristatic/tumoricidal
suppresses E2 dependent growth of breast AND uterine tissue; agonist in bone; lowers LDL
Raloxifene is a type ____ estrogen receptor modulator
Raloxifene is tumoristatic/tumoricidal
T/F tamoxifen increases risk of endometrial hyperplasia
T --> but raloxifene does not
anastrozole and exemestane MOA
inhibit action of aromatase--> tx of ER+ tumors
Indications for progestin therapy
replacement therapy, contraception/ivf, endometriosis, dysfunctional uterine bleeding
RU486 is a progesterone receptor type II _____
antagonist via a corepressor
Tx of hypogonadism
estrogens --> mestranol
Tx of ERT
Tx of osteoporosis
Tx of breast cancer
tamoxifen (SERM) and letrozole (aromatase inhibitor)