Direct biphasic effects of danazol on gonadotropin-dependent differentiation of cultured rat granulosa cells

Eli Y. Adashi, Carol E. Resnick
In: Fertility and Sterility · 1986 · vol. 45(6) , pp. 867–875 · doi:10.1016/s0015-0282(16)49408-2 · PMID:3086134 · W2415920529
article OA: closed CC0 ⤵ 2 in-corpus citations
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Danazol exerted biphasic effects on gonadotropin-dependent granulosa cell differentiation in culture, initially inhibiting and then promoting luteinization.

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Abstract

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.

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