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

Eli Y. Adashi, E Y Adashi, Carol E. Resnick, C E Resnick
Fertility and sterility · 1986 · vol. 45(6) , pp. 867–875 · doi:10.1016/s0015-0282(16)49408-2 · PMID:3086134 · W2415920529
Lab / animal 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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MeSH descriptors

Danazol Granulosa Cells Pregnadienes Animals Cell Differentiation Cell Differentiation Cells, Cultured Danazol DNA DNA Estrogens Estrogens Female Follicle Stimulating Hormone Follicle Stimulating Hormone Granulosa Cells Granulosa Cells Granulosa Cells Luteinizing Hormone Luteinizing Hormone

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