Human chorionic gonadotropin stimulation of estradiol production and androgen antagonism of gonadotropin-stimulated responses in cultured human granulosa-luteal cells.
Baseline and gonadotropin-stimulated estradiol production were examined in long term cultures of human granulosa-luteal cells isolated from women undergoing in vitro fertilization. Estradiol production declined by 70% during the first 48 h in culture and was minimally stimulated by the addition of hCG to the culture medium. During subsequent culture from 48-120 h estradiol production was significantly increased over control levels by hCG concentrations greater than 0.1 IU/ml. Incubation with testosterone stimulated estradiol production 100-fold in the presence and absence of gonadotropin. hCG (0.01-10 IU/ml) stimulated a 3- to 13-fold increase in progesterone production. However, at hCG concentrations greater than 1 IU/ml, coincubation with testosterone (10(-7) M) significantly inhibited progesterone production. Dihydrotestosterone also inhibited progesterone production, but to a lesser extent than testosterone. Freshly isolated granulosa-luteal cells specifically bound small amounts of [125I]hCG (less than 1,000 cpm/10(5) cells). Glycine buffer wash was shown to reversibly remove more than 88% of bound hCG and, in freshly isolated cells, increased [125I]hCG binding by 100%. In 5-day cultures, specific [125I] hCG binding nearly doubled from 52,000 cpm/10(5) cells in control cultures to 87,000 cpm/10(5) cells in cultures treated with hCG (0-5 IU/ml). At the highest concentration of hCG (5 IU/ml), testosterone (10(-7) M) significantly inhibited the amount of [125I]hCG specifically bound. In summary, estradiol production in long term cultures of granulosa-luteal cells appears to be gonadotropin dependent. In addition, the presence of testosterone (10(-7) M) antagonizes hCG-stimulated progesterone and LH receptor production by these cells.
D000728:Androgens / Q000494:pharmacology*; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D003338:Corpus Luteum / Q000378:metabolism*; D004958:Estradiol / Q000096:biosynthesis*; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008184:Luteal Cells / Q000187:drug effects / Q000378:metabolism*; D011374:Progesterone / Q000096:biosynthesis; D011956:Receptors, Cell Surface / Q000378:metabolism; D011974:Receptors, LH; D013739:Testosterone / Q000494:pharmacology
D000728:Androgens; D006063:Chorionic Gonadotropin; D011956:Receptors, Cell Surface; D011974:Receptors, LH; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol