PILOT PROJECT - FACTORS DETERMINING OBESITY-ASSOCIATED HYPERANDROGENEMIA IN GIRLS

多囊卵巢综合征(PCOS)是以高雄激素血症(HA)为特征的女性常见病 和排卵功能障碍。此外，多囊卵巢综合征与肥胖和其他代谢异常有关 (例如，胰岛素抵抗)。多囊卵巢综合征有多种病理生理机制。神经内分泌 异常在大多数患有多囊卵巢综合征的女性中扮演着重要的角色。多囊卵巢综合征与相对阻力有关 促性腺激素释放激素脉冲发生器对孕酮和雌二醇的负反馈： 这一缺陷似乎是HA的结果，也可能发生在HA青少年中。我们假设 青春期透明质酸可通过诱导下丘脑抵抗促进多囊卵巢综合征的发展 向负面反馈致敬。然而，青春期HA的病因仍不清楚。肥胖症是公认的 成人多囊卵巢综合征HA的病理生理因素；最近的数据表明，青春期周围肥胖是 与HA关联。然而，青春期肥胖和青春期肥胖之间关系的潜在机制 在肥胖女孩中观察到的雄激素的显著变异性是未知的。初步数据 这表明，肥胖的青春期前和青春期早期的高雄激素水平的女孩也表现出更大程度的 胰岛素抵抗与雄激素水平较低的肥胖女孩相比。该试点项目的目标1涉及详细的 评估肥胖青春期女孩的胰岛素抵抗和黄体生成素搏动性，其主要目标是 明确胰岛素抵抗在导致肥胖青春期女孩HA中的重要性。其次， 青春期肥胖相关透明质酸中促黄体生成素升高的作用将被评估。特征描述 青春期HA的潜在因素可以预测哪些青春期前和青春期早期的女孩会 随后会出现多囊卵巢综合征的症状。目标2的目标是调查其他可能 似乎直接对青春期女孩的HA有贡献，包括胰岛素样生长因子-L[IGF-I]，细胞因子， 还有脂肪因子。在这种情况下，将仔细评估潜在的混杂因素(例如，胰岛素、黄体生成素)。 该项目产生的数据将促使未来新的U54研究来研究复杂的相互作用 在导致多囊卵巢综合征的代谢和经典内分泌途径中。

Polycystic ovary syndrome (PCOS) is a common disorder of women marked by hyperandrogenemia (HA) and ovulatory dysfunction. Additionally, PCOS is associated with obesity and other metabolic abnormalities (e.g., insulin resistance). A number of pathophysiological mechanisms underlie PCOS. Neuroendocrine abnormalities play a significant role in most women with PCOS. PCOS is associated with relative resistance of the gonadotropin releasing hormone pulse generator to negative feedback by progesterone and estradiol: this defect appears to be a result of HA, and can also occur in adolescents with HA. We have hypothesized that peripubertal HA can promote the development of PCOS in part via induction of hypothalamic resistance to negative feedback. However, the cause of peripubertal HA remains unknown. Obesity is a well-recognized pathophysiological factor in the HA of adult PCOS; and recent data demonstrate that peripubertal obesity is associated with HA. However, the mechanisms underlying the relationship between peripubertal obesity and HA¿and the marked variability of androgens observed among obese girls¿are unknown. Preliminary data suggests that obese pre- and early pubertal girls with high androgen levels also exhibit greater degrees of insulin resistance compared to obese girls with lower androgens. Aim 1 of this pilot project involves detailed assessments of insulin resistance and LH pulsatility in obese peripubertal girls, and its primary goal is to define the importance of insulin resistance in causing HA in obese peripubertal girls. Secondarily, the contributions of elevated LH in obesity-associated HA across puberty will be assessed. Characterization of the factors underlying peripubertal HA may permit prediction of which pre- and early pubertal girls will subsequently go on to develop symptoms of PCOS. The goal of Aim 2 is to investigate other factors that may plausibly contribute directly to HA in peripubertal girls, including insulin-like growth factor-l [IGF-I], cytokines, and adipokines. In this setting, potential confounding factors (e.g., insulin, LH) will be carefully assessed. Data generated by this project will prompt novel future U54 studies to investigate the complex interactions among metabolic and classical endocrine pathways that lead to PCOS.