Phosphatidylinositol 3-kinase (EC 2.7.1.137 ) is composed of 85-kD (171833) and 110-kD subunits. The 85-kD subunit lacks PI3-kinase activity and acts as an adaptor, coupling the 110-kD subunit (p110) to activated protein tyrosine kinases.
General function
Comment
Cellular localization
Cytoplasmic
Comment
candidate123
Ovarian function
Follicle development
Comment
Expression regulated by
Growth Factors/ cytokines
Comment
Insulin Augmentation of 17{alpha}-Hydroxylase Activity Is Mediated by Phosphatidyl Inositol 3-Kinase But Not Extracellular Signal-Regulated Kinase-1/2 in Human Ovarian Theca Cells
Munir I, et al .
Polycystic ovary syndrome, characterized by hyperandrogenism and chronic anovulation, is frequently associated with insulin resistance. Ample evidence implicates a role for insulin in the genesis of ovarian hyperandrogenism. The objective of this study was to begin to define the intracellular signaling pathway(s) that mediates insulin regulation of 17alpha-hydroxylase activity in human ovarian theca cells. Third-passage theca cells, isolated from the ovaries of regularly cycling premenopausal women, were used. Insulin alone had no effect on 17alpha-hydroxylase activity or CYP17 mRNA expression but required costimulation with forskolin. At the insulin concentration used (10 ng/ml), a neutralizing antibody to the insulin receptor (but not an antibody to the type I IGF receptor) blocked the insulin stimulation of 17alpha-hydroxylase activity, demonstrating that the effects were mediated by the insulin receptor. Insulin stimulated both phosphatidylinositol-3-kinase (PI3-kinase) and extracellular signal-regulated kinase-1/2 (MAPK) pathways. Specific inhibition of MAPK kinase (MEK) with PD98059 or I0126 did not decrease the 17alpha-hydroxylase activity stimulated by forskolin or forskolin plus insulin. In contrast, the PI3-kinase inhibitor LY294002 completely blocked insulin-stimulated 17alpha-hydroxylase activity. Our data demonstrate that insulin stimulates PI3-kinase and extracellular signal-regulated kinase-1/2 activities in human theca cells, but only PI3-kinase mediates the insulin augmentation of forskolin-stimulated 17alpha-hydroxylase activity.
Ovarian localization
Theca
Comment
Follicle stages
Comment
Phenotypes
PCO (polycystic ovarian syndrome)
Mutations
1 mutations
Species: human
Mutation name: type: naturally occurring fertility: subfertile Comment:Detection and significance of phosphatidylinositol 3-kinase in adipose tissue of polycystic ovary syndrome patients with insulin resistance]. [Chu YL et al. (2006) To investigate the expression of phosphatidylinositol 3-kinase (PI-3K) in adipose tissue of polycystic ovary syndrome patients (PCOS), and explore molecular mechanisms of insulin resistance (IR) in PCOS. Samples from patients with PCOS with IR (n = 19), PCOS without IR (n = 10) and controls (n = 15) were collected. Serum fasting insulin (FIN) and fasting plasma glucose (FPG) were measured. Insulin resistance index was calculated using homeostasis model assessment (HOMA) to analyze the relationship between these markers and IR. Western blot technique was used to detect the PI-3K p85 subunit. Gene expression of PI-3K p85 subunit was detected by reverse transcription polymerase chain reaction (RT-PCR) method. Kinase activity was detected by immunoprecipitation, thin-layer chromatography and gamma scintillation counting. (1) The levels of FIN [(25.2 +/- 3.8) mU/L] and HOMA-IR (1.6 +/- 0.3) in PCOS with IR were significantly higher than those in PCOS without IR [(13.4 +/- 3.8) mU/L, 0.9 +/- 0.3] and controls [(9.5 +/- 2.6) mU/L, 0.5 +/- 0.3; all P < 0.05). (2) There was no significant difference in the protein (0.65 +/- 0.10) and gene expression (0.92 +/- 0.12) of PI-3K p85 subunit in PCOS with IR compared with PCOS without IR (0.72 +/- 0.10, 1.01 +/- 0.10) and control groups (0.73 +/- 0.14, 1.00 +/- 0.12; P > 0.05). (3) PI-3K activity in PCOS with IR (81%) and PCOS without IR (89%) was significantly decreased (P < 0.01, P < 0.05) and negatively correlated with HOMA-IR (r = -0.69, P < 0.01; r = -0.62, P < 0.05). No significant difference in the protein and gene expression of PI-3K p85 subunit in PCOS with IR is found. The decreased PI-3K activity may lead to IR of PCOS.//////////////////