Direct biphasic effects of danazol on gonadotropin-dependent differentiation of cultured rat granulosa cells.
The direct effects of danazol on granulosa cell differentiation were studied in vitro over a broad concentration range with a primary culture of rat granulosa cells. Whereas treatment with low-dose (defined herein as less than 10(-6) M) danazol by itself was without significant effect on basal steroid secretion, combined treatment with low-dose danazol (10(-7) M) and a minimally effective dose of follicle-stimulating hormone (FSH, 20 ng/ml) resulted in a substantial augmentation of the FSH effect. Although independent of the FSH dose employed, the effect of danazol proved dose- and time-dependent, with an apparent median effective dose of 3.6 +/- 0.3 X 10(-8) M. In contrast, high-dose danazol (defined herein as greater than 10(-6) M) produced dose-dependent inhibition of FSH (250 ng/ml)-supported steroid secretion. Taken together, our findings indicate that the effects of danazol on granulosa cell differentiation may be biphasic in nature, displaying a stimulatory low-dose component, followed by inhibition at higher dose levels.
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D003613:Danazol / Q000494:pharmacology*; D004967:Estrogens / Q000032:analysis; D005260:Female; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D006107:Granulosa Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D007986:Luteinizing Hormone / Q000494:pharmacology; D011245:Pregnadienes / Q000494:pharmacology*; D011374:Progesterone / Q000032:analysis; D011506:Proteins / Q000032:analysis; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013256:Steroids / Q000096:biosynthesis
D004967:Estrogens; D011245:Pregnadienes; D011506:Proteins; D013256:Steroids; D011374:Progesterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D004247:DNA; D003613:Danazol