Article

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

VA Medical Center, Witchita, Kansas, USA.
Endocrine (impact factor: 1.42). 07/2000; 12(3):315-21. DOI:10.1385/ENDO:12:3:315 pp.315-21
Source: PubMed

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.

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Keywords

Akt protein kinase activity
 
concentration-dependent manner
 
functional survival pathway
 
granulosa cell apoptosis
 
granulosa cells
 
IGF-I
 
IGF-I induced increases
 
IGF-I promotes survival
 
IGF-I treatment
 
IGF-I-induced phosphorylation
 
inactivation
 
Insulin-like growth factor-I
 
ovary
 
PI 3-kinase
 
PI 3-kinase activity
 
PI 3-kinase inhibitors wortmannin
 
PI 3-kinase/Akt signaling
 
porcine granulosa cells
 
survival factor
 
survival response
 

S D Westfall