• Shuffle
    Toggle On
    Toggle Off
  • Alphabetize
    Toggle On
    Toggle Off
  • Front First
    Toggle On
    Toggle Off
  • Both Sides
    Toggle On
    Toggle Off
  • Read
    Toggle On
    Toggle Off
Reading...
Front

Card Range To Study

through

image

Play button

image

Play button

image

Progress

1/77

Click to flip

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