Nestler J E
Division of Endocrinology and Metabolism, Medical College of Virginia, Virginia Commonwealth University, Richmond.
Horm Metab Res. 1989 May;21(5):258-60. doi: 10.1055/s-2007-1009207.
Hyperinsulinemia is known to reduce serum dehydroepiandrosterone sulfate (DHEA-S) levels in normal females. A possible mechanism for this phenomenon would be an insulin-mediated increase in steroid sulfatase activity, with insulin acting either via activation of the insulin receptor or via cross-reaction with the insulin-like growth factor I (IGF-I) receptor. Using a well characterized human cytotrophoblast system, the presence of steroid sulfatase activity in isolated cytotrophoblasts was documented. Half maximal cellular hydrolysis of DHEA-S was observed at a substrate concentration of 9.6-14.5 microM, and maximal hydrolysis at a concentration of 75-100 microM. The hypothesis that insulin increases steroid sulfatase activity was examined by exposing cytotrophoblasts to supraphysiological concentrations of either insulin (2 micrograms/ml) or IGF-I (20 ng/ml) for 24 h and then measuring the rate of DHEA-S hydrolysis. Insulin failed to affect cytotrophoblastic steroid sulfatase activity, irrespective of whether the substrate concentration was 20 microM or 100 microM. IGF-I also exerted no effect on steroid sulfatase activity. These data indicate that neither insulin nor IGF-I affect the steroid sulfatase activity of human cytotrophoblasts. An effect of insulin or IGF-I on the steroid-sulfatase activity of other tissues has not been excluded. These observations suggest that the decline in serum DHEA-S levels during hyperinsulinemia is not mediated via an insulin-induced increase in steroid sulfatase activity.
已知高胰岛素血症会降低正常女性血清硫酸脱氢表雄酮（DHEA-S）水平。这种现象的一种可能机制是胰岛素介导的类固醇硫酸酯酶活性增加，胰岛素可通过激活胰岛素受体或与胰岛素样生长因子I（IGF-I）受体发生交叉反应来发挥作用。利用一个特征明确的人细胞滋养层系统，记录了分离的细胞滋养层中类固醇硫酸酯酶活性的存在。在底物浓度为9.6 - 14.5微摩尔时观察到DHEA-S的半最大细胞水解，在浓度为75 - 100微摩尔时观察到最大水解。通过将细胞滋养层暴露于超生理浓度的胰岛素（2微克/毫升）或IGF-I（20纳克/毫升）24小时，然后测量DHEA-S水解速率，来检验胰岛素增加类固醇硫酸酯酶活性的假设。无论底物浓度是20微摩尔还是100微摩尔，胰岛素均未能影响细胞滋养层的类固醇硫酸酯酶活性。IGF-I对类固醇硫酸酯酶活性也无影响。这些数据表明，胰岛素和IGF-I均不影响人细胞滋养层的类固醇硫酸酯酶活性。胰岛素或IGF-I对其他组织类固醇硫酸酯酶活性的影响尚未排除。这些观察结果表明，高胰岛素血症期间血清DHEA-S水平的下降并非通过胰岛素诱导的类固醇硫酸酯酶活性增加介导。
