TY - JOUR
T1 - Adipocytes from women with polycystic ovary syndrome demonstrate altered phosphorylation and activity of glycogen synthase kinase 3
AU - Chang, Wendy
AU - Goodarzi, Mark O.
AU - Williams, Heith
AU - Magoffin, Denis A.
AU - Pall, Marita
AU - Azziz, Ricardo
N1 - Funding Information:
Supported in part by National Institutes of Health (Bethesda, MD) grants R03-HD42077, R01-HD29364, K24-HD01346-01, and M01-RR00425 and by the Helping Hand of Los Angeles (Los Angeles, CA).
PY - 2008/12
Y1 - 2008/12
N2 - 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)-3α and GSK3β in adipocytes; assessment of GSK3β activity. Result(s): Basal protein levels of glycogen synthase kinase (GSK3α and GSK3β) did not differ between control women and women with PCOS, nor did basal or insulin-stimulated levels of serine phosphorylated GSK3α. However, in adipocytes of women with PCOS, insulin stimulation was not associated with increased serine phosphorylation of GSK3β, in contrast to the case of control women. Tyrosine phosphorylation of GSK3β also was higher in women with PCOS, compared with in control women. Consistent with the phosphorylation data, GSK3β activity was elevated in PCOS adipocytes. Conclusion(s): These data suggest that GSK3β is hyperactivated and resistant to down-regulation by insulin in PCOS. By using physiologic approaches, we demonstrated that abnormal GSK3β 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.
AB - 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)-3α and GSK3β in adipocytes; assessment of GSK3β activity. Result(s): Basal protein levels of glycogen synthase kinase (GSK3α and GSK3β) did not differ between control women and women with PCOS, nor did basal or insulin-stimulated levels of serine phosphorylated GSK3α. However, in adipocytes of women with PCOS, insulin stimulation was not associated with increased serine phosphorylation of GSK3β, in contrast to the case of control women. Tyrosine phosphorylation of GSK3β also was higher in women with PCOS, compared with in control women. Consistent with the phosphorylation data, GSK3β activity was elevated in PCOS adipocytes. Conclusion(s): These data suggest that GSK3β is hyperactivated and resistant to down-regulation by insulin in PCOS. By using physiologic approaches, we demonstrated that abnormal GSK3β 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.
KW - Glycogen synthase kinase
KW - insulin resistance
KW - phosphorylation
KW - polycystic ovary syndrome
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U2 - 10.1016/j.fertnstert.2007.10.025
DO - 10.1016/j.fertnstert.2007.10.025
M3 - Article
C2 - 18178198
AN - SCOPUS:56649102159
SN - 0015-0282
VL - 90
SP - 2291
EP - 2297
JO - Fertility and sterility
JF - Fertility and sterility
IS - 6
ER -