Developmental Programming: Impact of Prenatal Testosterone Excess and Postnatal Weight Gain on Insulin Sensitivity Index and Transfer of Traits to Offspring of Overweight Females
Developmental Programming: Impact of Prenatal Testosterone Excess and Postnatal Weight Gain on Insulin Sensitivity Index and Transfer of Traits to Offspring of Overweight Females
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DOI：
10.1210/en.2009-1015
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发表时间：
2010-02-01
期刊：
影响因子：
4.8
通讯作者：
Herkimer, C.
中科院分区：
文献类型：
--
作者：
Padmanabhan, V.;Veiga-Lopez, A.;Herkimer, C.
多囊卵巢综合征（PCOS）是育龄妇女最常见的内分泌疾病，肥胖会使其恶化。母羊在妊娠第30-90天暴露于过量的睾酮（T），最终导致无排卵、功能性高雄激素血症、LH过量和多卵泡卵巢，这些特征与PCOS女性相似，有些生殖缺陷是由T的雄激素作用编程的，有些则不是。出生后体重增加过多会增加这些生殖缺陷的严重性。产前T治疗的母羊也表现出胰岛素敏感性降低，超过70%的PCOS妇女中发现了这一特征。我们测试的假设，降低胰岛素敏感性的产前T-治疗的母羊是由雄激素作用的T编程，过多的产后体重增加夸大了这一缺陷。此外，我们还测试了过度增重对胰岛素敏感性指数的破坏性影响是否会转移到雌性后代身上。采用静脉葡萄糖耐量试验评估胰岛素敏感性。结果显示，产前T过量对胰岛素敏感性的破坏性影响是由雄激素作用的T和出生后过度喂养受损的胰岛素敏感性在T-治疗和对照组，产前T-治疗的羊往往表现出这种过度喂养损伤早于对照组。重要的是，超重对照的后代也表现出胰岛素动力学缺陷，支持肥胖相关性状的代际转移。这些发现是相关的背景下，发展规划的胰岛素抵抗的产前类固醇和过量的体重增加。（内分泌学151：595-605，2010）
Polycystic ovary syndrome ( PCOS) is the most common endocrinopathy of reproductive-aged women and is exacerbated by obesity. Exposure of ewes to excess testosterone (T) from d 30-90 of gestation culminates in anovulation, functional hyperandrogenism, LH excess, and polyfollicular ovaries, features similar to those of women with PCOS, with some reproductive defects programmed by androgenic actions of T and others not. Excess weight gain during postnatal life increases the severity of these reproductive defects. Prenatal T-treated ewes also manifest reduced insulin sensitivity, a feature found in more than 70% of PCOS women. We tested the hypotheses that reduced insulin sensitivity of prenatal T-treated ewes is programmed by androgenic actions of T, and excess postnatal weight gain exaggerates this defect. In addition, we tested whether disruptive effects of excess weight gain on insulin sensitivity index are transferred to female offspring. Insulin sensitivity was assessed using iv glucose tolerance tests. Results revealed that disruptive effects of prenatal T excess on insulin sensitivity were programmed by androgenic action of T and postnatal overfeeding-impaired insulin sensitivity in both T-treated and controls and that prenatal T-treated sheep tend to manifest such overfeeding impairments earlier than controls. Importantly, offspring of overweight controls also manifest defects in insulin dynamics supportive of intergenerational transfer of obesity-related traits. The findings are of relevance in the context of developmental programming of insulin resistance by prenatal steroids and excess weight gain. (Endocrinology 151: 595-605, 2010)