Postnatal developmental consequences of altered insulin sensitivity in female sheep treated prenatally with testosterone.
Postnatal developmental consequences of altered insulin sensitivity in female sheep treated prenatally with testosterone.
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DOI：
10.1152/ajpendo.00107.2005
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发表时间：
2005-11
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通讯作者：
S. Recabarren;V. Padmanabhan;E. Codner;A. Lobos;C. Durán;M. Vidal;D. Foster;T. Sir-Petermann
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作者：
S. Recabarren;V. Padmanabhan;E. Codner;A. Lobos;C. Durán;M. Vidal;D. Foster;T. Sir-Petermann
产前睾酮（T）治疗的雌性绵羊表现出卵巢和内分泌学特征，类似于患有多囊卵巢综合征（PCOS）的女性，包括黄体生成素过量、多卵泡卵巢、功能性高雄激素血症和无排卵。在这项研究中，我们确定了产前T治疗对胰岛素敏感性指数（ISI）的发育影响，这是一个影响大多数PCOS妇女的变量。妊娠母羊从妊娠第30天至第90天每周两次肌内注射60 mg丙酸睾酮（溶于棉籽油）或溶剂[对照（C）]。出生时和5周龄时，T-雌性的体重低于C-雌性或雄性（P < 0.05）。T-雌性动物的肛门生殖器比例增加。在5、20和30周龄（n = 7-8/组）禁食过夜后进行的静脉内葡萄糖耐量试验和胰岛素耐量试验显示，C-雌性在5周龄时的ISI高于30周龄，反映了与青春期相关的胰岛素抵抗的发展。T-女性有较高的基础胰岛素水平，较高的空腹胰岛素-葡萄糖比，和较高的增量胰岛素曲线下面积的葡萄糖挑战。T-女性的ISI与男性相似。在20和30周龄时，两组间ISI无明显差异。在任何年龄组之间，平均基础血糖浓度和葡萄糖消失和摄取没有差异。我们的研究结果表明，产前T治疗导致后代出生体重下降和出生后早期胰岛素敏感性受损。
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.