Effect of clomiphene isomers on progestin synthesis in cultured human granulosa cells

Abstract

The effect of en-clomiphene and zu-clomiphene (10⁻⁹–10⁻⁵ M) on progestin synthesis in cultured human granulosa cells was studied under basal conditions and in the presence of LH (100 ng/ml). Granulosa cells were obtained from either pre-ovulatory follides of clomiphene-HMG-stimulated cycles or from large follicles of mid-to-late follicular phase of spontaneous cycles. The basal and LH-stimulated progesterone accumulation was dose-dependently reduced by en- and zu-clomiphene (10⁻⁶–10⁻⁵ M) in cells from both groups studied, an effect similar to that of oestradiol. In contrast to oestradiol, both en- and zu-clomiphene (10⁻⁶–10⁻⁵ M) reduced the basal and LH-stimulated pregnenolone accumulation in cells of stimulated cycles. The effect of clomiphene on progesterone, and pregnenolone accumulation was more pronounced in LH-stimulated cells than under basal conditions. There were no qualitative differences between the two isomers and the results were principally the same in cells from both groups of follicles studied. It is concluded that en-clomiphene and zu-clomiphene have similar inhibitory effects on progestin synthesis in human granulosa cells in vitro.