Lean women with polycystic ovary syndrome respond to insulin reduction with decreases in ovarian P450c17 alpha activity and serum androgens.
Lean women with polycystic ovary syndrome respond to insulin reduction with decreases in ovarian P450c17 alpha activity and serum androgens.
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DOI：
10.1210/jcem.82.12.4431
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发表时间：
1997-12
期刊：
影响因子：
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通讯作者：
J. Nestler;D. Jakubowicz
中科院分区：
文献类型：
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作者：
J. Nestler;D. Jakubowicz
目前尚不清楚高胰岛素血症是否在正常体重或消瘦女性的多囊卵巢综合征（PCOS）发病机制中起作用。有证据表明，这些妇女是胰岛素抵抗和高胰岛素血症，这项研究的目的是检验假设，高胰岛素血症刺激卵巢细胞色素P450 c17 α活性的非肥胖妇女PCOS，从而增加血清雄激素浓度。我们评估了31名非肥胖PCOS女性口服二甲双胍（500 mg）或安慰剂（每日3次，持续4-6周）前后的卵巢P450 c17 α活性（通过测量17 α-羟孕酮对GnRH激动剂的反应）、空腹血清类固醇和口服葡萄糖耐量。在19名接受二甲双胍治疗的女性中，口服葡萄糖后血清胰岛素曲线下面积的平均值（+/- SE）从44 +/- 5降至24 +/- 3 nmol/L.min（P = 0.003）。基础血清17 α-羟孕酮从3.4 +/- 0.3 nmol/L降至2.5 +/- 0.4 nmol/L（P = 0.05），GnRH刺激的峰值血清17 α-羟孕酮从12.2 +/- 1.6 nmol/L降至7.5 +/- 0.7 nmol/L（P = 0.005）。安慰剂组的血清17 α-羟孕酮值没有变化。二甲双胍组中，血清游离睾酮从18.2 +/- 3.1降至5.5 +/- 0.7 pmol/L（P < 0.001），降低70%，血清性激素结合球蛋白从84 +/- 6升高至134 +/- 15 nmol/L（P = 0.002）。安慰剂组的这些数值均无变化。这些结果表明，高胰岛素血症刺激卵巢P450 c17 α活性的非肥胖妇女PCOS。他们还指出，二甲双胍降低血清胰岛素可降低卵巢细胞色素P450 c17 α活性，并改善这些女性的高雄激素血症。
It is unknown whether hyperinsulinemia plays a role in the pathogenesis of polycystic ovary syndrome (PCOS) in normal weight or thin women. Evidence indicates that these women are insulin resistant and hyperinsulinemic, and this study was conducted to test the hypothesis that hyperinsulinemia stimulates ovarian cytochrome P450c17 alpha activity in nonobese women with PCOS, thereby increasing serum androgen concentrations. We assessed ovarian P450c17 alpha activity (by measuring the response of 17 alpha-hydroxyprogesterone to a GnRH agonist), fasting serum steroids, and oral glucose tolerance before and after oral administration of either metformin (500 mg) or placebo three times daily for 4-6 weeks in 31 nonobese women with PCOS. In the 19 women given metformin, the mean (+/- SE) area under the serum insulin curve after oral glucose administration decreased from 44 +/- 5 to 24 +/- 3 nmol/L.min (P = 0.003). Basal serum 17 alpha-hydroxyprogesterone decreased from 3.4 +/- 0.3 to 2.5 +/- 0.4 nmol/L (P = 0.05), and GnRH-stimulated peak serum 17 alpha-hydroxyprogesterone decreased from 12.2 +/- 1.6 to 7.5 +/- 0.7 nmol/L (P = 0.005). Serum 17 alpha-hydroxyprogesterone values did not change in the placebo group. In the metformin group, serum free testosterone decreased by 70% from 18.2 +/- 3.1 to 5.5 +/- 0.7 pmol/L (P < 0.001), and serum sex hormone-binding globulin increased from 84 +/- 6 to 134 +/- 15 nmol/L (P = 0.002). None of these values changed in the placebo group. These findings suggest that hyperinsulinemia stimulates ovarian P450c17 alpha activity in nonobese women with PCOS. They also indicate that decreasing serum insulin with metformin reduces ovarian cytochrome P450c17 alpha activity and ameliorates the hyperandrogenism of these women.