Growth hormone, insulin-like growth factor I, and leptin interaction in human cultured lutein granulosa cells steroidogenesis

Objective: To investigate the effect of leptin on the actions of growth hormone (GH) and insulin-like growth factor-I (IGF-I) in ovarian steroidogenesis in vitro. Design: In vitro cell culture study. Setting: Research laboratory of a university hospital. Patient(s): Luteinized granulosa cells (GC) were obtained from 20 healthy women undergoing ovarian stimulation for IVF treatment. Intervention(S): Granulosa cells were cultured in serum free conditions for 72 hours with either GH or IGF-I, or their combination, in the absence or presence of leptin (1, 10, and 100 ng/mL). Main Outcome Measure(s): At 24 and 72 hours of the culture estradiol (E-2) and progesterone. (P) concentrations were measured in culture supernatants by enzyme immunoassays. Result(S): Leptin at the doses of 1 and 10 ng/mL significantly stimulated, whereas at the dose of 100 ng/mL it significantly suppressed E-2 and P production as compared to control. Estradiol production was significantly stimulated by both GH (72 hours) and IGF-I (24 and 72 hours) and that of P only by IGF-I (72 hours). Leptin at the low doses enhanced, whereas at the high dose it suppressed the effect of GH or IGF-I on E-2 and P synthesis. Conclusion(S): These results demonstrate for the first time that leptin can modulate the effect of GH on steroids production by human luteinized GC in culture.