Effects of danazol on steroidogenesis and gonadotropic responsiveness in isolated human preovulatory follicular cells.
In order to investigate the influence of danazol on steroidogenesis and gonadotropic responsiveness of human follicular cells, granulosa and thecal cells of preovulatory follicles were isolated and separately incubated for short term periods. Human chorionic gonadotropin (hCG) (100 IU/ml), FSH (0.5 IU/ml) and danazol (10 micrograms/ml) alone or in combination were added to the incubation medium. Following incubation the cellular cyclic adenosine 3'5' monophosphate (cAMP) levels and the medium content of progesterone (P), androstenedione (A) and 17 beta-estradiol (E2) were determined. All follicles included in the study were classified as nonatretic and well developed, i.e. less than 3 days before ovulation. Human chorionic gonadotropin caused an increase in cAMP formation in both cell-types and this effect was significantly counteracted by danazol in vitro. In granulosa cells danazol tended to counteract a stimulatory effect of FSH on cAMP formation. No significant influence of danazol was found on the basal steroid formation of both cell types during short term incubation. On the other hand, danazol significantly counteracted the FSH stimulated P formation of the granulosa cells and the hCG stimulated A and E2 formation of the thecal cells. It is concluded that danazol inhibits gonadotropin-stimulated steroidogenesis locally in the human follicular cells and that this effect of danazol is mediated via the cyclic AMP system.
D000328:Adult; D000735:Androstenedione / Q000096:biosynthesis*; D002478:Cells, Cultured; D006063:Chorionic Gonadotropin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000242:Cyclic AMP / Q000096:biosynthesis; D003613:Danazol / Q000008:administration & dosage / Q000494:pharmacology*; D004958:Estradiol / Q000096:biosynthesis*; D005260:Female; D005640:Follicle Stimulating Hormone / Q000037:antagonists & inhibitors / Q000494:pharmacology; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D006080:Ovarian Follicle / Q000187:drug effects* / Q000378:metabolism; D011245:Pregnadienes / Q000494:pharmacology*; D011374:Progesterone / Q000096:biosynthesis*; D013799:Theca Cells / Q000187:drug effects / Q000378:metabolism
D006063:Chorionic Gonadotropin; D011245:Pregnadienes; D000735:Androstenedione; D011374:Progesterone; D004958:Estradiol; D005640:Follicle Stimulating Hormone; D000242:Cyclic AMP; D003613:Danazol