Insulin and insulin-like growth factor I stimulate the proliferation of human ovarian theca-interstitial cells

OBJECTIVE: To determine whether insulin and insulin-like growth factor I (IGF-I) affect the proliferation of human theca-interstitial cells. DESIGN: In vitro assays. SETTING: University laboratory. PATIENT(S): Premenopausal women undergoing oophorectomy for benign conditions. INTERVENTION(S): Purified theca-interstitial cells were cultured in chemically defined media with or without insulin and IGF-I. MAIN OUTCOME MEASURE(S): The proliferation of cells was evaluated by determination of [3H] thymidine incorporation and cell counting. RESULT(S): Insulin and IGF-I stimulated DNA synthesis by theca-interstitial cells in a dose-dependent fashion. Insulin-like growth factor I had a greater potency than did insulin. The effects of both approached, but did not reach, the level of DNA synthesis observed in cultures exposed to 10% fetal bovine serum. Direct counting of theca-interstitial cells revealed that IGF-I significantly increased the total number of cells (36% above control), whereas insulin induced a modest and statistically nonsignificant increase in the cell number (14% above control). CONCLUSION(S): The present results support the hypothesis that insulin and IGF-I promote the mitotic activity of theca-interstitial cells. These effects may represent mechanisms that lead to hyperplasia of the thecal/stromal compartment in polycystic ovary syndrome.