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  • Title: Selective impairment in glycogen synthase kinase-3 and mitogen-activated protein kinase phosphorylation: comparisons with the hyperandrogenic and the hyperinsulinemic rats.
    Author: Chen Y, Qiao J, Yan LY, Huang S, Zhao PL, Yan J.
    Journal: Fertil Steril; 2009 Oct; 92(4):1447-1455. PubMed ID: 19027112.
    Abstract:
    OBJECTIVE: To characterize and compare the effect of DHEA and insulin plus hCG on ovarian morphology, estrous cycle, hormonal levels, insulin sensitivity, and the regulation of insulin signaling in rats. DESIGN: Animal model study. SETTING: University laboratory. ANIMAL(S): Female Sprague-Dawley rats. INTERVENTION(S): Female rats received DHEA or insulin plus hCG by continuous administration. MAIN OUTCOME MEASURE(S): Ovarian morphology, estrous cycle, hormonal levels, insulin sensitivity, protein levels, and phosphorylation state of glycogen synthase kinase-3beta and extracellular regulated kinase 1/2 in the ovary. RESULT(S): Rats treated with DHEA displayed anovulation, insulin resistance, and polycystic ovaries characterized by cysts and a diminished granulosa layer. In contrast, insulin plus hCG results in acyclicity with increasing androgen biosynthesis and ovarian morphology different from that in DHEA-treated rats. Moreover, we found that insulin-stimulated serine-phosphorylation of glycogen synthase kinase-3beta was higher in insulin plus hCG-treated rats but lower in DHEA-treated rats. Furthermore, basal and insulin-stimulated tyrosine-phosphorylation of extracellular regulated kinase 1/2 was higher in DHEA-treated rats than in controls. CONCLUSION(S): Notwithstanding that both the hyperandrogenism and the hyperinsulinemia synergistic with hCG-treated rats displayed the typical traits of human polycystic ovary syndrome, there is a divergence in the insulin-signaling pathway in the ovarian tissue, which may have a role in the pathogenesis of polycystic ovary syndrome.
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