Moghetti P, Castello R, Negri C, Tosi F, Spiazzi G G, Brun E, Balducci R, Toscano V, Muggeo M
Division of Endocrinology and Metabolic Diseases, University of Verona, Italy.
J Clin Endocrinol Metab. 1996 Mar;81(3):881-6. doi: 10.1210/jcem.81.3.8772544.
Recent data suggest that insulin is a modulator of ovarian and adrenal steroidogenesis and that, in the ovary of hyperandrogenic women, hyperinsulinemia might cause dysregulation of cytochrome P450c17 alpha activity. To further assess in vivo the effects of insulin on adrenal steroidogenesis, ACTH stimulation was carried out in 21 hyperandrogenic women during a 3-h hyperinsulinemic (80 mU/m2-min) euglycemic clamp. In all of these women the procedure was repeated during saline infusion as n control. In nonamenorrheic patients, the tests were performed in the early follicular phase of two different menstrual cycles. Serum cortisol, progesterone, 17-hydroxypregnenolone (17-OHJPREG). 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone (DHEA), and androstenedione (A) were measured after 2 h of insulin or saline infusion (zero time) and, subsequently, 30 and 60 min after an iv bolus of 0.25 mg ACTH-(1-24). At zero time, no difference was found in the serum steroid concentrations between the two protocols. ACTH-stimulated serum 17-OHPREG and, to a lesser extent, 17-OHP were significantly higher during insulin than during saline infusion (peaks, 60.6 +/- 9.0 vs. 40.7 +/- 7.9 and 7.7 +/- 7.7 vs. 6.6 +/- 0.6 nmol/L; P < 0.005 and P < 0.01, respectively). Serum DHEA was also slightly higher during hyperinsulinemia, although only after 30 min (54.5 +/- 3.0 vs. 48.2 +/- 4.2 nmol/L; P < 0.05). No statistically significant difference in the cortisol, progesterone, or androstenedione response to ACTH was found between the two protocols. ACTH-stimulated 17-OHPREG/DHEA and 17-OHP/A molar ratios, indexes of apparent 17,20-lyase activity, were significantly higher during the clamp studies than during saline infusion (by ANOVA, F = 12.8; P < 0.001 and F = 6.7; P < 0.005, respectively), suggesting an impaired enzyme activity. These in vivo data support the hypothesis that insulin potentiates ACTH-stimulated steroidogenesis. This effect of insulin seems to be associated with a relative impairment of 17,20-lyase activity.
近期数据表明，胰岛素是卵巢和肾上腺类固醇生成的调节因子，在雄激素过多的女性卵巢中，高胰岛素血症可能导致细胞色素P450c17α活性失调。为了进一步在体内评估胰岛素对肾上腺类固醇生成的影响，对21名雄激素过多的女性进行了促肾上腺皮质激素（ACTH）刺激试验，试验期间进行3小时的高胰岛素血症（80 mU/m²·分钟）正常血糖钳夹。在所有这些女性中，作为对照，在输注生理盐水期间重复该操作。对于非闭经患者，在两个不同月经周期的卵泡早期进行测试。在输注胰岛素或生理盐水2小时（零时）后，随后在静脉推注0.25 mg ACTH-（1-24）后30分钟和60分钟，测量血清皮质醇、孕酮、17-羟孕烯醇酮（17-OHJPREG）、17-羟孕酮（17-OHP）、脱氢表雄酮（DHEA）和雄烯二酮（A）。零时，两种方案之间的血清类固醇浓度没有差异。ACTH刺激后，胰岛素输注期间血清17-OHJPREG以及程度稍轻的17-OHP显著高于生理盐水输注期间（峰值分别为60.6±9.0与40.7±7.9以及7.7±7.7与6.6±0.6 nmol/L；P分别<0.005和P<0.01）。高胰岛素血症期间血清DHEA也略有升高，尽管仅在30分钟后（54.5±3.0与48.2±4.2 nmol/L；P<0.05）。两种方案之间在皮质醇、孕酮或雄烯二酮对ACTH的反应方面未发现统计学上的显著差异。ACTH刺激后的17-OHPREG/DHEA和17-OHP/A摩尔比（表观17,20-裂解酶活性指标）在钳夹研究期间显著高于生理盐水输注期间（通过方差分析，F = 12.8；P<0.001和F = 6.7；P<0.005），表明酶活性受损。这些体内数据支持胰岛素增强ACTH刺激的类固醇生成这一假说。胰岛素的这种作用似乎与17,20-裂解酶活性的相对受损有关。
