Mechanism by which 17 beta-estradiol inhibits ovarian androgen production in the rat.
The mechanism by which 17 beta-estradiol inhibits ovarian androgen biosynthesis was investigated. Immature 25-day-old rats were treated for 2 days with estradiol, after which whole ovaries were dispersed, and gonadotropin binding and cAMP and steroid hormone production were examined. When dispersed cells from untreated control ovaries were incubated with hCG (100 ng/ml), there were marked increases (10-fold) in steroid production, with the major steroids being progesterone and androstenedione. The stimulation of steroidogenesis by hCG was dose-related (ED50 = 100 pg/ml hCG). After 2 days of estradiol treatment, the maximum hCG stimulation of androstenedione, testosterone, 17 alpha-hydroxypregnenolone, and 17 alpha-hydroxyprogesterone production by ovarian cells was inhibited by 90%; pregnenolone production was unchanged, while progesterone production was increased by 30%. Time course studies showed that the stimulatory effect of hCG on androgen production was maximally inhibited (90%) after 12 h of estradiol treatment. Implanting miniestradiol capsules unilaterally under the ovarian bursa caused a 77% decrease in the hCG stimulation of androgen production by the estradiol-treated cells, while progesterone production was unchanged. hCG-stimulated steroidogenesis in the contralateral ovary was not altered. Estradiol treatment did not affect the binding capacity, the hCG stimulation of cAMP production, or the number of steroid-producing cells in the ovaries. It is concluded from these experiments that exogenous estradiol acts directly on the rat ovary to abolish the hCG stimulation of androgen production by rapidly inhibiting 17 alpha-hydroxylation.
D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000728:Androgens / Q000096:biosynthesis*; D000818:Animals; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D010053:Ovary / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D011974:Receptors, LH; D013997:Time Factors
D000728:Androgens; D006063:Chorionic Gonadotropin; D011956:Receptors, Cell Surface; D011974:Receptors, LH; D004958:Estradiol; D000242:Cyclic AMP; D015096:3-Hydroxysteroid Dehydrogenases; D000469:Alkaline Phosphatase