Insulin sensitivity and cardiovascular risk factors in ovariectomized monkeys with estradiol alone or combined with nomegestrol acetate
Insulin sensitivity and cardiovascular risk factors in ovariectomized monkeys with estradiol alone or combined with nomegestrol acetate
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DOI：
10.1210/jc.83.3.896
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发表时间：
1998-03-01
影响因子：
5.8
通讯作者：
Cefalu, WT
中科院分区：
文献类型：
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作者：
Wagner, JD;Thomas, MJ;Cefalu, WT
我们以前已经表明，醋酸甲羟孕酮（MPA），无论是单独或结合马雌激素（CEE），显着降低胰岛素敏感性（SI），与未经处理的对照组和那些与CEE单独处理。本研究的目的是确定雌二醇（E-2）与醋酸诺美孕酮（NA;一种缺乏雄激素活性的强效炔雌醇）合用和不合用对SI和动脉抗氧化活性（通过F-2-异前列腺素测定）的影响。对36只成年雌性食蟹猴（Macaca fascicularis）进行卵巢切除，并喂食中度致动脉粥样硬化饮食，饮食中添加以下三种处理之一，持续12周：1）无处理（对照）; 2）E-2;或3）连续组合E-2 + NA（E-2 + NA）。治疗10周后，使用第三时相胰岛素输注，通过频繁采样的静脉葡萄糖耐量试验评估SI和葡萄糖有效性。治疗12周后，测量胸主动脉中的胆固醇含量和F-2-异前列腺素。与对照组或E-2 + NA治疗组相比，E-2治疗组的SI显著更高（10.03 +/- 0.91 vs. 6.35和6.49 x 10（-4）min（-1）mu U（-1）mL; P < 0.05）。与我们对CEE和MPA的研究相反，E-2 + NA治疗虽然将SI降低到低于E-2组的SI，但并没有将SI降低到低于对照猴的SI。正如预期的那样，短时间治疗导致主动脉胆固醇含量无显著差异。对总F-2-异前列烷（代表主要由自氧化引起的F-2-异前列烷形成）无给药效应，表明抗氧化活性极低。然而，前列腺素F-2 α（PGF（2 α））异构体（一种由花生四烯酸自氧化和环氧合酶活性形成的前列腺素（PG）异构体）存在治疗差异。与对照组相比，E-2处理的PGF（2 α）浓度低32%，与E-2 + NA处理相比低36%（0.48 +/- 0.08对0.71 +/- 0.12和0.75 +/- 0.06; P < 0.05），表明激素处理之间PG合成的差异。总之，NA，一种没有雄激素活性的雌激素，可能仍然会影响一些心血管危险因素，与仅用雌激素治疗不同。但是，它似乎比MPA危害更小。
We have previously shown that medroxyprogesterone acetate (MPA), either alone or combined with conjugated equine estrogens (CEE), significantly decreased insulin sensitivity (SI), compared with both untreated controls and those treated with CEE alone. The purpose of this study was to determine the effects of estradiol (E-2), with and without nomegestrol acetate (NA; a potent progestin that lacks androgenic activity), on SI and arterial antioxidant activity, as determined by F-2-isoprostanes. Thirty-six adult female cynomolgus monkeys (Macaca fascicularis) were ovariectomized and fed a moderately atherogenic diet, with one of the following three treatments added to the diet, for 12 weeks: 1) no treatment (control); 2) E-2; or 3) continuous combined E-2 + NA (E-2 + NA). SI and glucose effectiveness were assessed by the frequently sampled iv glucose tolerance test using a third-phase insulin infusion after 10 weeks of treatment. Cholesterol content and F-2-isoprostanes were measured in the thoracic aorta after 12 weeks of treatment. E-2 treatment resulted in a significantly greater SI, compared with control or E-2 + NA-treated monkeys (10.03 +/- 0.91 vs. 6.35 and 6.49 x 10(-4) min(-1) mu U(-1)mL; P < 0.05). In contrast to our studies of CEE and MPA, E-2 + NA treatment, though reducing the SI below that of the E-2 group, did not reduce the SI below that of control monkeys. As expected, the short period of treatment resulted in no significant differences in aortic cholesterol content. There was no treatment effect on total F-2-isoprostanes (representing F-2-isoprostane formation caused primarily by autooxidation), suggesting minimal antioxidant activity. However, there was a treatment difference in the prostaglandin F-2 alpha (PGF(2 alpha)) isomer (a prostaglandin (PG) isomer formed by both autooxidation of arachidonate and cyclooxygenase activity). PGF(2 alpha) concentrations were 32% lower with E-2 treatment, compared with controls, and 36% lower, compared with E-2 + NA treatment (0.48 +/- 0.08 vs. 0.71 +/- 0.12 and 0.75 +/- 0.06; P < 0.05), suggesting differences in PG synthesis between hormone treatments. In conclusion, NA, a progestin without androgenic activity, may still affect some cardiovascular risk factors differently than estrogen-only therapy. However, it seems to be less detrimental than MPA.