Influence of dehydroepiandrosterone on the expression of insulin-like growth factor-1 during cystogenesis in polycystic rat ovaries and in cultured rat granulosa cells.

This study was designed to investigate the expression of insulin-like growth factor-1 (IGF-1) during cystogenesis in the dehydroepiandrosterone (DHEA)-induced rat polycystic ovarian syndrome (PCO) model. IGF-1 expression patterns in DHEA-treated rat ovaries were compared with those in control ovaries. In situ hybridization revealed a similar distribution of IGF-1 mRNA in DHEA-treated and control ovaries: in both, IGF-1 mRNA expression was confined to the granulosa cells of preantral and small antral follicles. Some hybridization signals for IGF-1 mRNA were also found in theca and infrequently in the interstitial cells. No signal was observed in larger antral follicles, atretic follicles, or cysts. This similarity indicates that there might be a shared mechanism in the early follicular development of normal folliculogenesis and DHEA-induced cystogenesis. The effects of DHEA on granulosa cells were analyzed in vitro in their quiescent, proliferative, differentiative, and preovulatory stages. Northern analysis revealed three transcripts for IGF-1 (7.5 kilobases [kb], 1.6 kb, and a group of signals between 0.4 and 0.9 kb) in cells at all stages except the preovulatory. The strongest signal was observed in cells of the proliferative stage of control cultures, while expression of IGF-1 increased only in the DHEA-treated cells cultured in the differentiative stage (when they secrete estrogen). Increase in IGF-1 expression may contribute to the hypersteroidogenism observed in the DHEA-treated rat PCO model.