Steroidogenesis in vitro of human granulosa-luteal cells pretreated in vivo with gonadotropin-releasing hormone analogs.

A modulatory role for gonadotropin-releasing hormone (GnRH) on granulosa cell functions has been demonstrated in animals. Because human granulosa cells have specific receptors for GnRH, we have compared steroidogenesis in vitro of cells pretreated in vivo with GnRH analogs (GnRH-a) with other ovarian stimulation regimens used in in vitro fertilization (IVF) cycles. Cells from 13 patients treated with a GnRH-a for 26.8 +/- 1.1 days during pituitary desensitization and ovarian stimulation with gonadotropins were cultured. Their steroidogenesis was evaluated in basal conditions as well as after stimulation with follicle-stimulating hormone (FSH) and human chorionic gonadotropin (hCG). Granulosa-luteal cells from 9 women treated with a combination of clomiphene citrate (CC) and gonadotropins were also cultured. Estradiol production in response to FSH was stimulated only in the GnRH-a-treated cells. Basal, FSH-, and hCG-induced progesterone (P) accumulation was higher in the CC-treated cells. The peak of P production was delayed 2 days in the GnRH-a-treated group. Only cells pretreated in vivo with GnRH-a accumulated 20 alpha-hydroxyprogesterone in culture. The results of the present study suggest that the use of GnRH-a during a long period of time for IVF affects the steroidogenic pathway of human granulosa-luteal cells. It seems that, at least in part, this change is due to the stimulation of the metabolizing enzyme 20 alpha-hydroxysteroid dehydrogenase by GnRH-a.