Direct inhibitory effect of estrogen on LH-stimulated androgen synthesis by ovarian cells cultured in defined medium

Abstract

The direct inhibitory effect of estrogen on ovarian androgen synthesis was investigated. When primary cultures of rat ovarian theca-interstitial cells were grown in defined medium with LH there was a marked increase in androgen synthesis of which 98% was androsterone (control = 11 ± 2 ng; LH = 1219±217 ng/ml/10 6 cells). Diethylstilbestrol (DES), estrone (E 1), estradiol (E 2), and estriol (E 3) inhibited LH-stimulated androsterone synthesis by 81%, 81%, 81%, and 47%, respectively. The ED 50's of the estrogens were: DES = 4.2±2. l × 10 −9M; E 1 = E 2 = 9.5±2.4 × 10 −8 M; and E 3 = 3.8±2.6 × 10 −7 M. The estrogen effect was very rapid ( t 1 2 = 10 min) and long-lasting. Metabolic studies revealed that estrogen inhibited androsterone, androstenedione, 5α-androstane-3α, 17β-diol, and testosterone accumulation by 80%, dehydroepiandrosterone and 17α-hydroxypregnenolone by 40%, 17α-hydroxyprogesterone by 30%, while pregnenolone and progesterone were unchanged. These results prove, for the first time, that estrogen can directly inhibit LH-stimulated androgen production in ovarian theca-interstitial cells and suggest that mechanism involves, at least in part, a rapid selective inhibition of the 17α-hydroxylase/C 17–20 desmolase activities.