Selective impairment in glycogen synthase kinase-3 and mitogen-activated protein kinase phosphorylation: comparisons with the hyperandrogenic and the hyperinsulinemic rats.

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.