Putative role of the phosphatidylinositol 3-kinase-Akt signaling pathway in the survival of granulosa cells.

Insulin-like growth factor-I (IGF-I) is an important differentiation and survival factor for granulosa cells. The purpose of this study was to test the hypothesis that IGF-I promotes survival of porcine granulosa cells by signaling through the phosphatidylinositol (PI) 3-kinase/Akt signal transduction pathway. Treatment with IGF-I (100 ng/mL) for 10 min stimulated PI 3-kinase and Akt protein kinase activity. IGF-I stimulated the phosphorylation and activation of Akt in a time- and concentration-dependent manner. The PI 3-kinase inhibitors wortmannin and LY294002 blocked IGF-I induced increases in PI 3-kinase activity and phosphorylation of Akt. Additionally, IGF-I treatment prevented apoptosis. The survival response to IGF-I was blocked by treatment with either wortmannin or LY294002. These data suggest that IGF-I-induced phosphorylation of Akt is mediated through PI 3-kinase and that inactivation of this pathway results in granulosa cell apoptosis. We conclude that the PI 3-kinase/Akt signaling serves as a functional survival pathway in the ovary.