title: Putative role of the phosphatidylinositol 3-kinase-Akt signaling pathway in the survival of granulosa cells.
abstract: 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.
authors.affiliation: VA Medical Center, Witchita, Kansas, USA.
authors.forename: S D
authors.initials: SD
authors.lastname: Westfall
authors.forename: I R
authors.initials: IR
authors.lastname: Hendry
authors.forename: K L
authors.initials: KL
authors.lastname: Obholz
authors.forename: B R
authors.initials: BR
authors.lastname: Rueda
authors.forename: J S
authors.initials: JS
authors.lastname: Davis
mesh_terms: D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D053938:DNA Fragmentation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006107:Granulosa Cells / Q000166:cytology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D007700:Kinetics; D009025:Morpholines / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction; D013552:Swine; D000077191:Wortmannin
chemical_list: D000730:Androstadienes; D002867:Chromones; D004247:DNA; D004791:Enzyme Inhibitors; D007334:Insulin-Like Growth Factor I; D009025:Morpholines; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D000077191:Wortmannin; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one