We randomized 32 cycling female Sprague-Dawley rats (82 days old) into experimental and control groups (16 animals/group). Hyperinsulinemia was induced and maintained for 22 days in the experimental group with NPH human insulin (Novolin, Squibb-Novo, Princeton, NJ) as previously described. Controls received an identical volume of vehicle. Fifteen minutes before death, each rat received a sc injection of 100 ng synthetic GnRH (Factrel, Ayerst Laboratories, New York, NY). The mean serum insulin level was significantly higher in the insulin-treated group than in the control group (165 ± 57 vs. 49 ± 9 μU/ml; P < 0.05). The mean final weight also was significantly higher in the insulin-treated group (283 ± 4 vs. 242 ± 7 g; P < 0.001). There were no significant differences in mean final serum levels of testosterone, estradiol, estrone, or androstenedione or in GnRH-stimulated serum levels of LH or FSH. The androstenedione to estrone ratio, however, was significantly lower in the insulin-treated group (2.5 ± 0.3 vs. 3.4 ± 0.2; P < 0.01), suggesting that aromatase activity increased with hyperinsulinemia. Specific [125I] insulin binding to ovarian tissue homogenates was lower in the insulin-treated group (1.7 ± 0.1% vs. 2.6 ± 0.6%/ 0.2 mg protein; P > 0.05), suggesting that ovarian insulin receptors tended to down-regulate with hyperinsulinemia. Specific [125I]insulin-like growth factor I ([125I]IGF-I) binding to ovarian tissue homogenates, in contrast, was significantly higher in the insulin-treated group (13.3 ± 1.4% vs. 7.2 ± 0.6%/0.2 mg protein; P < 0.05), suggesting that ovarian IGF receptors up-regulated with hyperinsulinemia. The affinity of neither [125I] insulin binding nor that of [125I]IGF-I binding changed significantly, with the 50% inhibition point remaining between 2.0 and 5.0 ng/ml for each peptide in both groups. We conclude that hyperinsulinemia increases ovarian [125I]IGF-I binding and stimulates aromatase activity in the rat. These phenomena, if also true in women, could be important factors contributing to the ovarian hyperstimulation observed in various hyperinsulinemic states.
ASJC Scopus subject areas