Regulation of insulin-like growth factor binding protein secretion by human granulosa luteal cells in a polycystic ovary-like environment

Abstract

Objective: To determine the effect of androstenedione (A), insulin, and LH on secretion of insulin-like growth factor binding proteins (IGFBPs) from human granulosa luteal cells. Design: Human granulosa cells were cultured for a total of 4 days in serum-free medium containing A (10 −6 mol/L), with or without insulin (100 μU/mL–800 μU/mL), LH (1 μU/mL–10 μg/L), and A (10 −5 mol/L). Setting: Granulosa cells were obtained from IVF procedures. Patient(s): Women undergoing IVF for tubal disease. Intervention(s): None. Main Outcome Measure(s): Immunoassay and autoradiographs of Western ligand blotting detected IGFBP accumulations in the medium. Result(s): Cultured granulosa cells secreted IGFBP-1 through IGFBP-4. Insulin (100 μU/mL–800 μU/mL), LH (1 μg/L–10 μg/L), and A (10 −5 mol/L) caused a significant decrease in IGFBP-1 accumulation in the medium both alone and when added in combination. The release of IGFBP-2 and IGFBP-4 was significantly stimulated by insulin, whereas LH had no effect. Elevated levels of androgen (10 −5 mol/L) significantly stimulated the secretion of IGFBP-2, whereas the release of IGFBP-4 was reduced. Conclusion(s): These results demonstrate that androgen and insulin are important regulators of IGFBP release and that elevated levels of the two hormones may contribute to the altered IGFBP profile found in PCOS follicles, compared with the case of estrogen-dominant follicles.