Hyperandrogenism and Insulin Resistance in the Ontogeny of PCOS

多囊卵巢综合征(PCOS)是女性最常见的内分泌疾病，临床表现为 临床上有无排卵性不孕症。在女孩中，早熟可能是多囊卵巢综合征的最早迹象。许多 患有多囊卵巢综合征的妇女和早熟的女孩也有胰岛素抵抗，这是一种表型特征。 这两种情况都有共性。家族聚集性似乎是多囊卵巢综合征的一个特征，我们之前的工作已经 证明高雄激素血症和胰岛素抵抗是可传播的特征，我们假设 患有多囊卵巢综合征的女性的女儿可能在青春期中期患上高雄激素血症， 高胰岛素血症，19号染色体上候选等位基因的传递预示着风险。我们建议 多囊卵巢综合征妇女女孩与非多囊卵巢综合征妇女女孩的病例/对照纵向研究 为青春期精心配对。我们将对这些女孩进行多囊卵巢综合征相关异常的表型鉴定 并跟随他们度过青春期的后期阶段。我们提供了令人信服的初步数据来支持我们的 这些研究的假设和可行性。此外，青春期这些异常的个体发育 转换有助于了解胰岛素抵抗和高雄激素血症在病因中的作用 这将通过二甲双胍在女孩身上的双盲随机对照试验来进一步测试 有早熟的阴毛。这些研究旨在为确定可能发育的女孩提供基础。 多囊卵巢综合征和无排卵性不孕症，并使制定预防策略。我们的具体目标是： 为了解多囊卵巢综合征患者女儿的雄激素状况及其与高胰岛素血症的时间关系， 记录胰岛素增敏对改善高雄激素血症和高胰岛素血症的效果 并检测遗传标记对女性早熟的预测能力。 多囊卵巢综合征的发展和对二甲双胍的反应。这些研究对世界银行的几个关键目标很重要 U54生殖中心的任务包括：1)女性的病因、病理生理和预防 多囊卵巢综合征引起的不孕不育，特别强调那些基于遗传的疾病，以及2) 利用基因组学开发新的、非侵入性的生殖疾病和障碍诊断方法

Polycystic Ovary Syndrome (PCOS), which is the most common endocrinopathy in women, presents clinically with anovulatory infertility. In girls, premature pubarche may be the earliest sign of PCOS. Many women with PCOS and girls with premature pubarche are also insulin resistant, a phenotypic characteristic common to both conditions. Familial clustering appears to be a feature of PCOS and our previous work has demonstrated that hyperandrogenism and insulin resistance are transmissible traits, We hypothesize that daughters of women with PCOS are likely to develop hyperandrogenism in mid puberty, exacerbated by hyperinsulinemia, and that transmission of a candidate allele on Chromosome 19 predicts risk. We propose a case/control longitudinal study of girls of women with PCOS compared to girls of women without PCOS, carefully matched for pubertal stage. We will phenotype these girls for abnormalities associated with PCOS and follow them through later pubertal stages. We present compelling preliminary data supporting our hypotheses and the feasibility of these studies. Further, the ontogeny of these abnormalities in the pubertal transition provides insight into the contributions of insulin resistance and hyperandrogenemia to the etiology of the syndrome, that will be further tested by a double blind randomized controlled trial of metformin in girls with premature pubarche. These studies are intended to provide a basis for identifying girls likely to develop PCOS and anovulatory infertility and to enable development of preventive strategies. Our specific aims are: to examine androgen status in daughters of women with PCOS and its temporal relation to hyperinsulinemia, to document the effects of insulin sensitization on improvement in hyperandrogenism and hyperinsulinemia in girls with premature pubarche, and to examine the predictive ability of genetic markers on the development of PCOS and response to metformin. These studies are important to several key goals of the U54 Reproductive Center mission including: 1) the etiology, pathophysiology, and prevention of female infertility due to PCOS, with particular emphasis on those conditions that are genetically based, and 2) the use of genomics to develop novel, non-invasive diagnostics for reproductive diseases and disorder