Jakubowicz D J, Nestler J E
Department of Internal Medicine, Hospital de Clinicas Caracas, Venezuela.
J Clin Endocrinol Metab. 1997 Feb;82(2):556-60. doi: 10.1210/jcem.82.2.3753.
Insulin resistance and increased ovarian cytochrome P450c17 alpha activity (i.e. increased 17 alpha-hydroxylase and, to a lesser extent, increased 17,20-lyase) are both features of the polycystic ovary syndrome (PCOS). Evidence suggests that hyperinsulinemia may stimulate ovarian P450c17 alpha activity in obese women with PCOS. We hypothesized that weight loss would decrease serum insulin and P450c17 alpha activity in PCOS. Therefore, we measured serum steroid concentrations and 17 alpha-hydroxyprogesterone responses to leuprolide administration and performed oral glucose tolerance tests before and after 8 weeks of a hypocaloric diet in 12 obese women with PCOS (PCOS group) and 11 obese women with normal menses (control group). Serum insulin decreased in both groups. In the PCOS group, basal serum 17 alpha-hydroxyprogesterone decreased from 4.2 +/- 0.6 to 3.0 +/- 0.5 nmol/L (P < 0.05), and leuprolide-stimulated peak serum 17 alpha-hydroxyprogesterone decreased from 14.9 +/- 2.6 to 8.9 +/- 0.8 nmol/L (P < 0.025). Serum testosterone decreased from 2.47 +/- 0.52 to 1.56 +/- 0.33 nmol/L (P < 0.05), and free testosterone decreased from 9.03 +/- 1.39 to 5.95 +/- 0.50 pmol/L (P < 0.02). None of these values changed in the control group. Serum sex hormone-binding globulin increased by 4.5- and 3-fold in the PCOS (P < 0.003) and control (P < 0.007) groups, respectively. We conclude that dietary weight loss decreases ovarian P450c17 alpha activity and reduces serum free testosterone concentrations in obese women with PCOS, but not in obese ovulatory women. The changes in women with PCOS may be related to a reduction in serum insulin.
胰岛素抵抗和卵巢细胞色素P450c17α活性增加（即17α-羟化酶增加，以及程度较轻的17,20-裂解酶增加）都是多囊卵巢综合征（PCOS）的特征。有证据表明，高胰岛素血症可能会刺激患有PCOS的肥胖女性的卵巢P450c17α活性。我们假设体重减轻会降低PCOS患者的血清胰岛素和P450c17α活性。因此，我们测量了12名患有PCOS的肥胖女性（PCOS组）和11名月经正常的肥胖女性（对照组）在低热量饮食8周前后的血清类固醇浓度以及对亮丙瑞林给药的17α-羟孕酮反应，并进行了口服葡萄糖耐量试验。两组的血清胰岛素均下降。在PCOS组中，基础血清17α-羟孕酮从4.2±0.6降至3.0±0.5 nmol/L（P<0.05），亮丙瑞林刺激后的血清17α-羟孕酮峰值从14.9±2.6降至8.9±0.8 nmol/L（P<0.025）。血清睾酮从2.47±0.52降至1.56±0.33 nmol/L（P<0.05），游离睾酮从9.03±1.39降至5.95±0.50 pmol/L（P<0.02）。对照组的这些值均未改变。PCOS组和对照组的血清性激素结合球蛋白分别增加了4.5倍和3倍（P<0.003和P<0.007）。我们得出结论，饮食减肥可降低患有PCOS的肥胖女性的卵巢P450c17α活性并降低血清游离睾酮浓度，但对肥胖有排卵功能的女性则无此作用。PCOS女性的这些变化可能与血清胰岛素的降低有关。
