Adipocytes from women with polycystic ovary syndrome demonstrate altered phosphorylation and activity of glycogen synthase kinase 3

作者：Chang Wendy; Goodarzi Mark O; Williams Heith; Magoffin Denis A; Pall Marita; Azziz Ricardo^*

来源：Fertility and Sterility, 2008, 90(6): 2291-2297.

DOI：10.1016/j.fertnstert.2007.10.025

• Glycogen synthase kinase
• polycystic ovary syndrome
• phosphorylation
• insulin resistance

Objective: To test. the hypothesis that an abnormality in glycogen synthase kinase-3 (GSK3) is a pathogenic factor in polycystic ovary syndrome (PCOS).
Design: Prospective experimental study (adipocytes).
Setting: Tertiary-care academic medical center and teaching hospital.
Patient(s): Twenty patients with PCOS and 21 healthy control women.
Intervention(s): Blood sampling, physical exam, biopsy of SC lower abdominal fat.
Main Outcome Measure(S): Glucose transport and protein levels and phosphorylation state of glycogen synthase kinase (GSK)-3 alpha and GSK3 beta in adipocytes; assessment of GSK3 beta activity.
Result(s): Basal protein levels of glycogen synthase kinase (GSK3 alpha and GSK3 beta) did not differ between control women and women with PCOS, nor did basal or insulin-stimulated levels of serine phosphorylated GSK3 alpha. However, in adipocytes of women with PCOS, insulin stimulation was not associated with increased serine phosphorylation of GSK3 beta, in contrast to the case of control women. Tyrosine phosphorylation of GSK3 beta also was higher in women with PCOS, compared with in control women. Consistent with the phosphorylation data, GSK3 beta activity was elevated in PCOS adipocytes.
Conclusion(s): These data Suggest that GSK3 beta is hyperactivated and resistant to down-regulation by insulin in PCOS. By using physiologic approaches, we demonstrated that abnormal GSK3 beta regulation is a potential mechanism for the insulin resistance that is seen in some women with PCOS, which may contribute to their development of the syndrome. (Fertil Steril (R) 2008;90:2291-7.

• 出版日期2008-12