Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
77 Cards in this Set
- Front
- Back
gonadarche
|
change of ovarian fxn at puberty; periodic bleeding begins ~1 yr after
|
|
estrogen-mimetic cmpds
|
flavonoids
|
|
major estrogens produced by women
|
estradiol (E2), estrone (E1), and estriol (E3); most estrone and estriol produced in liver from estradiol or in peripheral tissues from androstenedione and other androgens
|
|
what produces estrogen in ovary
|
theca and granulosa cells in first part of cycle and luteinized granulosa and theca cells of corrpus luteum after ovulation (biosynthesis slightly different)
|
|
what produces estrogens in pregnancy
|
fetal adrenal zone (secretes androgen precursor), placenta (aromatizes it into estrogen)
|
|
range of estrogen levels in serum of women with regular cycle
|
50 pg/ml to 350-850 pg/ml
|
|
most important effect of synthetic alterations of estrogens
|
oral availability
|
|
what does estradiol bind when released into circulation
|
strongly to alpha2 globulin (sex hormone-binding globulin (SHBG)) and lower affinity to albumin; relatively unavailable for diffusion into cells when bound
|
|
estradiol in liver
|
converted to estrone and estriol and their 2-hydroxylated derivatives and conjugated metabolites=excreted in bile
|
|
undesirable hepatic effects of estrogens
|
synthesis of increased clotting factors and plasma renin substrate; can be minimized by avoiding first-pass effect (vaginal, transdermal, injection)
|
|
where are estrogen receptors found
|
predominately in nucleus bound to heat-shock proteins that stabilize them; binding releases hstabilizing proteins
|
|
what does receptor-hormone complex form and bind
|
homodimers that bind to estrogen response elemets (EREs) in promoters of various genes
|
|
ERE structure
|
2 half-sites arranged as a palindrome separated by a small gourp of nucleotides called the spacer
|
|
what rapid estrogen effects do not require gene activation
|
granulosa cell Ca2+ uptake and increased uterine blood flow=via intracellular signaling pathways
|
|
estrogens and bone
|
decrease rate of resoption of bone by promoting apoptosis of osteoclasts and antagonizing osteoclastogenic and pro-osteoclastic effects of PTH and IL-6
|
|
what metabolic alterations does estrogen cause in liver
|
higher circulating level of proteins like transcortin, thyroxine-binding globulin, SHBG, transferrin, renin substrate, and fibrinogen; leads to increased circulating levels of thyroxine, estrogen, testosterone, iron, copper, and other substances
|
|
estrogens and lipids
|
increase HDL and slight reduction in LDL; reduction in total plasma cholesterol; plasma triglycerides levels increased
|
|
primary hypogonadism clinical uses of estrogen
|
primary failure of ovary dvlp, premature menopause, castration, or menopause
|
|
lipid in menopause
|
LDL increases, HDL remains higher than men (relatively unaffected), VLDL and lipoprotein and triglycerides relatively unaffected
|
|
uterine bleeding and estrogens
|
major cause of postmenopausal uterine bleeding
|
|
cancer and estrogens
|
small increase breast cancer with prolonged use; increase endometrial cancer when estrogens taken alone
|
|
what is progesterone a percursor to
|
estrogens, androgens, and adrenocortical steroids
|
|
third generation progestins
|
19-nor, 13-ehtyl; used primarily in oral contraceptives and claimed to lower androgenic activity compared to older progestins; desogestrel, gestodene, and norgestimate
|
|
progesterone in liver
|
metabolized to pregnanediol and conjugated with glucuronic acid; excreted in urine as pregnanediol glucuroonide
|
|
effects of progesterone
|
stimulates lipoprotein lipase and seems to favor fat deposition; increases basal insulin levels and insulin response to glucose; promotes glycogen storage in liver and promotes ketogenesis
|
|
progesterone in kidney
|
can compete with aldosterone for mineralcorticoid receptor of renal tubule causeing decrease Na+ reabsorption (causes increased aldosterone secretion)
|
|
progesterone and breast
|
alveolobular dvlp of secretory apparatus
|
|
diagnostic use of progesterone
|
test of estrogen secretion; administer for 5-7 days=followed by withdrawal bleeding in amenorrheic patients only when endometrium has been stimulated by estrogens
|
|
androgens ovaries produce in small amounts
|
testosterone, androstenedione, and dehydroepiandrosterone
|
|
inhibin produced by ovary
|
inhibits FSH secretion (alpha-beta dimer)
|
|
activin produced by ovary
|
increases FSH secretion (beta-beta dimer)
|
|
relaxin produced by ovary
|
2 chains linked by disulfide bonds cleaved from a prohormone; produced in luteinized granulosa cells of corpus luteum; increase glycogen synthesis and water uptake by myometrium and decreases uterine contractility
|
|
2 types of preparations used for oral contraception
|
1) combo estrogen and progestins 2) continuous progestin therapy without estrogens
|
|
combo estrogen and progesterone contraception divisions
|
monophasic (constant dosage of both), biphasic or triphasic (dose of one or both changes once or twice during cycle)
|
|
how do combo contraceptions work
|
selective inhibition of pituitary fxn that results in inhibition of ovulation; also produce change in cervical mucus, uterine endometrium, and motility and secretion of uterine tubes
|
|
normal menstration after termination of oral contraceptives
|
75% ovulate in first posttreatment cycle, 97% by 3rd; 2% amenorrheic for up to several years
|
|
cervix and prolonged oral contraceptive use
|
some hypertrophy and polyp formation
|
|
19-nor progestins and endometrium
|
tend to produce more glandular atrophy and usually less bleeding
|
|
contraceptives and blood clotting
|
increase in factors 7, 8, 9, 10, and decrease in antithromin III
|
|
estrogens and bile
|
reduces flow of bile; proportion of cholic acid in bile increases while chenodeoxycholic acid decreases
|
|
heart and oral contraceptives
|
small increases in CO associated with higher systolic and diastolic BP and HR
|
|
chloasma
|
increase pigment of skin
|
|
why are increased sedimentation rates thought to be caused by with oral contraceptives
|
due to increased levels of fibrinogen
|
|
most common problem in using progestational agents alone for contraception
|
breakthrough bleeding in up to 25%
|
|
why do aome antibiotics interfere with oral contraceptives
|
GI flora increase enterohepatic cycling and bioavailability of estrogens; also may stimulate liver metabolism of estrogens (rifampin)
|
|
when is contraception with progestins useful
|
hepatic disease, hypertension, psychosis, mental retardation, or prior thromboembolism
|
|
Mifepristone
|
antagonist at progesterone and glucocorticoid receptors-has luteolytic effect and is effective as postcoital contraceptive
|
|
mifepristone plus prostaglandin
|
effective abortifacient; 95% in first 7 weeks of pregnancy
|
|
tamoxifen
|
competative partial agonist inhibitor of estradiol at the estrogen receptor; first selective estrogen receptor modulator (SERM)
|
|
metabolism of tamoxifen
|
primarily liver excretion
|
|
other SERMs
|
toremifene, raloxifene(doesn't stimulate endometrium or breast), clomiphene (ovulation inducing)
|
|
mifepristone specs
|
19-norsteroid that binds strongly to progesterone receptor and inhibits activity; MOA unknown
|
|
danazol
|
weak progestational, androgenic, and glucocorticoid activities; used to suppress ovarian fxn-inhibits midcycle surge in LH and FSH (doesn't lower basal LH or FSH levels in normal women)
|
|
danazol metabolism
|
feces and urine; half-life >15 hours
|
|
major use of danazol
|
endometriosis; also fibrocystic disease of breast and hematologic or allergic disorders (hemophilia, Christmas disease, idiopathic thrombocytopenic purpura, and angioneurotic edema)
|
|
danazol and pregnancy/breast feeding
|
may cause urogenital abnormalities
|
|
anastrozole
|
selective nonsteroidal inhibitor of aromatase (required for estrogen synthesis); letrozole similar
|
|
exemestane
|
steroid molecule; irreversible inhibitor of aromatase
|
|
fulvestrant
|
pure estrogen receptor antagonist
|
|
clomiphene specs
|
partial estrogen agonist; urine excretion; ovulation-inducing agent; 10% incidence of multiple pregnancy
|
|
clomiphene MOA
|
partial agonist at estrogen receptors-leads to increase secretion of gonadotropins and estrogens by inhibiting estradiol's neg feedback effect on gonadotropins
|
|
source of estradiol in seminiferous tubules
|
Sertoli cells-aromatization of locally produced testosterone
|
|
what produces testosterone in males
|
interstitial or Leydig cells-stimulated by LH
|
|
active proteins synthesized and secreted by Sertoli cells
|
mullerian duct inhibitory factor, inhibin, and activin
|
|
what is responsble for feedback inhibition of pituitary FSH in men
|
inhibins with testosterone and dihydrotestosterone
|
|
what do target tissues convert testosterone to
|
dihydrotestosterone by 5a-reductase
|
|
what tissues convert testosterone to estrodiol by P450 aromatase
|
adipose, liver, and lypothalamus
|
|
metabolic effects of androgens on liver
|
reduction of hormone binding and other carrier proteins, increase liver synthesis of clotting factors, triglyceride lipase, a1-antitrypsin, haptoglobin, and sialic acid; also stimulates renal erythropoietin secretion and decreases HDL levels
|
|
ketoconazole specs
|
inhibitor of adrenal and gonadal steroid synthesis; primarily used as anti-fungal
|
|
ketoconazole MOA
|
displaces estrdiol and dihydrotestosterone from SHBP in vitro and increases the estradiol:testosterone ratio in plasma in vivo with different mechanism
|
|
inhibition of 17-hydroxylation of progesterone to pregnenolone
|
prevents action of side-chain splitting enzyme and further transformation of steroid precursors to active androgens; cmpd thus far too toxic for use
|
|
Finateride
|
steroid-like inhibitor of 5a-reductase; half excreted in feces; reduce prostate in men with BPH; alternative is dutasteride
|
|
cyproterone and cyproterone acetate specs
|
antiandrogens that inhibit action at target organ; used in hirtuism and excessive sex drive
|
|
flutamide specs
|
potent antiandrogen used in prostatic carcinoma; not a steroid-behaves like competative antagonist at androgen receptor
|
|
why can flutamide cause muld gynecomastia
|
increase testicular estrogen production
|
|
Bicalutamide and nilutamide specs
|
potent orally active antiandrogens; metastatic carcinoma of prostate
|
|
spironolactone specs
|
competative inhibitor of aldosterone, also competes with dihydrotestosterone for androgen receptors in target tissues; also reduces 17a-hydroxylase activity; treatment of hirtuism in women
|