Recabarren Sergio E, Padmanabhan Vasantha, Codner Ethel, Lobos Alejandro, Durán Claudio, Vidal Mónica, Foster Douglas L, Sir-Petermann Teresa
Laboratory of Animal Physiology and Endocrinology, Faculty of Veterinary Medicine, Univ. of Concepción, Chillán, Chile.
Am J Physiol Endocrinol Metab. 2005 Nov;289(5):E801-6. doi: 10.1152/ajpendo.00107.2005.
Prenatally testosterone (T)-treated female sheep exhibit ovarian and endocrinological features that resemble those of women with polycystic ovarian syndrome (PCOS), which include luteinizing hormone excess, polyfollicular ovaries, functional hyperandrogenism, and anovulation. In this study, we determined the developmental impact of prenatal T treatment on insulin sensitivity indexes (ISI), a variable that is affected in a majority of PCOS women. Pregnant ewes were treated with 60 mg testosterone propionate intramuscularly in cottonseed oil two times a week or vehicle [control (C)] from days 30 to 90 of gestation. T-females weighed less than C-females or males (P < 0.05) at birth and at 5 wk of age. T-females had an increased anogenital ratio. An intravenous glucose tolerance test followed by an insulin tolerance test conducted after an overnight fast at 5, 20, and 30 wk of age (n = 7-8/group) revealed that ISI were higher at 5 than 30 wk of age in C-females, reflective of a developing insulin resistance associated with puberty. T-females had higher basal insulin levels, higher fasting insulin-to-glucose ratio, and higher incremental area under the insulin curve to the glucose challenge. The ISI of T-females was similar to that of males. No differences in ISI were evident between groups at 20 and 30 wk of age. Mean basal plasma glucose concentrations and glucose disappearance and uptake did not differ between groups at any age. Our findings suggest that prenatal T treatment leads to offspring with reduced birth weight and impaired insulin sensitivity in early postnatal life.
产前接受睾酮（T）处理的雌性绵羊表现出与多囊卵巢综合征（PCOS）女性相似的卵巢和内分泌特征，包括促黄体生成素过多、多囊卵巢、功能性雄激素过多和无排卵。在本研究中，我们确定了产前T处理对胰岛素敏感性指数（ISI）的发育影响，ISI是大多数PCOS女性中受影响的一个变量。在妊娠第30至90天，怀孕母羊每周两次肌肉注射60毫克丙酸睾酮于棉籽油中，或注射赋形剂[对照组（C）]。T处理的雌性在出生时和5周龄时体重低于C处理的雌性或雄性（P<0.05）。T处理的雌性肛门生殖比增加。在5、20和30周龄时（每组n = 7 - 8），过夜禁食后进行静脉葡萄糖耐量试验，随后进行胰岛素耐量试验，结果显示C处理的雌性在5周龄时的ISI高于30周龄，这反映了与青春期相关的胰岛素抵抗的发展。T处理的雌性基础胰岛素水平更高、空腹胰岛素与葡萄糖比值更高，并且在葡萄糖刺激后胰岛素曲线下的增量面积更大。T处理的雌性的ISI与雄性相似。在20和30周龄时，各组之间的ISI没有明显差异。在任何年龄，各组之间的平均基础血浆葡萄糖浓度、葡萄糖消失和摄取均无差异。我们的研究结果表明，产前T处理导致后代出生体重降低，并且在出生后早期生活中胰岛素敏感性受损。
