Leptin inhibits gonadotrophin-stimulated granulosa cell progesterone production by antagonizing insulin action

Recent evidence has demonstrated that expression of leptin and leptin receptors is expected in the human ovary, and that leptin alters ovarian steroidogenesis in animal models. This study was designed to determine whether leptin modulates basal, gonadotrophin-, and insulin-stimulated progesterone production by human luteinized granulosa cells (GC). GC were recovered from follicular aspirates obtained during transvaginal ultrasound-guided oocyte retrieval for in-vitro fertilization-embryo transfer, and cultured in defined medium with various combinations of chorionic gonadotrophin (HCG; 0 or 100 ng/ml), insulin (0-30 μg/ml), and leptin (0-100 ng/ml). Progesterone concentrations in media were determined at various time points (2 h to 6 days). Leptin time- and dose-dependently inhibited (P < 0.05) HCG-stimulated progesterone production by human luteinized GC, but did not alter basal steroidogenesis. Moreover, the inhibitory effect of leptin on gonadotrophin-stimulated progesterone production was only manifested in the presence of insulin. Leptin suppression of insulin-supported steroidogenesis was also time- and dose-dependent. We conclude that leptin inhibits gonadotrophin-stimulated GC progesterone production apparently by antagonizing insulin action. Leptin suppression of progesterone production by human luteinized GC is consistent with recent data from animal models, and supports the possible role of leptin as a regulator of human ovarian function.