THE EFFECTS OF EXPERIMENTAL HYPERINSULINEMIA ON STEROID-SECRETION, OVARIAN [I-125] INSULIN BINDING, AND OVARIAN [I-125] INSULIN-LIKE GROWTH-FACTOR-I BINDING IN THE RAT
THE EFFECTS OF EXPERIMENTAL HYPERINSULINEMIA ON STEROID-SECRETION, OVARIAN [I-125] INSULIN BINDING, AND OVARIAN [I-125] INSULIN-LIKE GROWTH-FACTOR-I BINDING IN THE RAT
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DOI：
10.1210/endo-122-2-581
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发表时间：
1988-02-01
期刊：
影响因子：
4.8
通讯作者：
DUNAIF, A
中科院分区：
文献类型：
--
作者：
PORETSKY, L;GLOVER, B;DUNAIF, A
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 .mu.U/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.
