Hypothalamic Pituitary Gonadal Axis and Sexual Differentiation Flashcards
function of estradiol/estrogen
growth, puberty, decreasing FSH and LH except just before ovulation when estradiol levels rise sharply and become positive feedback for LH
function of testosterone
growth, puberty, decrease FSH
function of progesterone
supports pregnancy
what does inhibin do
decrease FSH (specifically)
what does activin do
increase FSH (specifically)
what does anti mullerian hormone do?
sexual differentiation: absence of it makes female internal repro develop. (suppresses development of mullerian ducts and prevents female internal development in male)
what structure is conserved through 4 different hormones
alpha subunit identical in TSH, LH, FSH, and hCG
what is the 2nd messenger for TSH, LH, FSH, and hCG
cAMP
how is GnRH produced
as a pre-pro-GnRH, then native GnRH 10AA because in hypothalamic hypophyseal portal system
what is the female pattern of LH release
surge and tonic (surges for ovulation)
what is the male pattern of LH release
tonic (no ovulation)
what occurs during male brain development
testosterone crosses BBB and is aromatized to estrogen quickly. there is estrogenic effects in the male which causes the surge center to NOT develop
what occurs during the female brain development
during development, estrogens from placenta and ovary of developing fetus and mothers ovary release estradiol. is lipophilic and travels through the body. in the female, estradiol is bound to alpha-fetoprotein which prevents it from crossing BBB. no estradiol effect in the brain so the surge center develops.
regulation of testosterone
negative feedback only from testosterone to hypothalamus and pituitary
regulation of estrogen
mostly negative regulation to hypothalamus and pituitary except when about to ovulate
what does the dominant follicle display
LH and FSH receptors
what do other follicles display
only FSH receptors
what does testosterone and inhibin do?
inhibit GnRH, LH, and FSH
what does progesterone, estradiol and inhibin do
inhibit GnRH, LH, FSH
what does estradiol alone (increased concentration) do
stimulates GnRH, LH and FSH
initiates LH surge
what do luteal cells secrete during luteal phase
estrogen, progesterone to maintain pregnancy
“pro-gestation hormone”
what does LH do
stimulates cholesterol desmolase to start cholesterol forming pregnenolone (eventually to estradiol and testosterone)
what does FSH do in the female
stimulates aromatase to make estradiol from testosterone
what is the primary circulating form of testosterone
dihydrotestosterone
what does increase in GnRH at age 8 do
triggers release of FSH and LH from anterior pituitary which then triggers test and estradiol
compare before and after puberty
hypothalamus and pituitary are sensitive to testosterone and estradiol. sensitivity decreases allowing high concentration of steroids to stimulate secondary sex characteristics
effects of estradiol
continuation of folliculogenesis and secondary sex characteristics
effects of testosterone
initiation of spermatogenesis and secondary sex characteristics
what occurs during menopause
FSH is increased more than LH because no influence of estrogens or progesterones from corpus luteum
what occurs during senescence in males
testosterone decreases but sperm capacity and production doesn’t change
what do sertoli cells secrete
antimullerian hormone, inhibin, androgen binding protein
what do leydig cells secrete
testosterone
what does FSH stimulate
sertoli cells to produce inhibin to negatively feedback AP
what does LH stimulate
leydig cells to make testosterone, direct negative feedback on hypothalamus and AP. acts paracrine on sertoli cells to make inhibin to negative feedback.
male 2 cell two gonadotropin complex
- hypothalamus releases GnRH, stimulates AP to secrete LH and FSH.
- LH stimulates leydig cells to release testosterone.
- FSH stimulates sertoli cells to release androgen binding protein and inhibin.
- ABP binds to testosterone, keeping it at a high concentration.
- inhibin is released by sertoli cells, negative feedback to AP.
- testosterone negative feedback to hypo and pituitary.
what does ABP do
causes conformational change in chemistry of testosterone, causes it to become less lipophilic, maintains increased concentration in testis
paracrine control of testosterone
what receptors are on the thecal cells
LH
what receptors are on granulosa cells
FSH preselection then LH (dominant follicle)
female 2 cell 2 gonadotropin complex
theca interna responds to LH only–>cAMP–>PKA–>cholesterol to testosterone.
testosterone freely crosses to the granulosa cell.
FSH and LH bind to receptors and increase cAMP and PKA to make testosterone into estradiol. estradiol goes into bloodstream.
describe thecal cells
responsive to LH, produce androstenedione (testosterone goes to granulosa cells)
describe granulosa cells
avascular, preselection responds to FSH alone and produces some estradiol and inhibin.
after selection, responsive to FSH and LH, produces substantial estradiol
what do luteal cells do during luteal phase
progesterone and estradiol send negative feedback to hypothalamus and AP (if not pregnant)
what determines female differentiation
no Y chromosome, no SRY gene, no TDF protein, no AMH (internal), no testosterone (external) == girl
what determines male differentiation
Y chromosome, SRY gene, TDF protein, AMH by sertoli cells, leydig cells making testosterone == boy
what is directly responsible for growth of prostate and penis?
DHT
when does sexual differentiation occur
6-10weeks
male and female puberty difference
female puberty happens earlier than males
hypergonadotropic hypogonadism
high FSH and LH, low sex steroids
hypogonadotropic hypogonadism
low FSH and LH, low sex steroids
secondary is more common bc tumors, head trauma, drugs, disease, disorder
hypogonadotropic hypergonadism
low FSH and LH, high sex steroids
gonad tumors, hyperplasia
hypergonadotropic hypergonadism
high FSH and LH and sex steroids
precocious puberty, pituitary/gonad tumors?
