PILOT PROJECT - FACTORS DETERMINING OBESITY-ASSOCIATED HYPERANDROGENEMIA IN GIRLS

多囊卵巢综合征（PCOS）是一种常见的以高雄激素血症（HA）为特征的女性疾病 和排卵功能障碍此外，PCOS与肥胖和其他代谢异常有关 (e.g.,胰岛素抵抗）。多囊卵巢综合征的病理生理机制很多。神经内 异常在大多数患有PCOS的女性中起着重要作用。PCOS与相对抵抗力有关 的促性腺激素释放激素脉冲发生器的负反馈的孕酮和雌二醇： 这种缺陷似乎是HA的结果，也可能发生在患有HA的青少年中。我们假设 青春期前HA可能通过诱导下丘脑阻力而促进PCOS的发生 消极的反馈。然而，青春期周围HA的原因仍然未知。肥胖是一个公认的 在成人PCOS HA的病理生理因素;和最近的数据表明，青春期周围肥胖是 与HA有关。然而，青春期前后肥胖和肥胖症之间关系的潜在机制， 在肥胖女孩中观察到的HA和雄激素的显著变异性尚不清楚。初步数据 表明，肥胖的青春期前和早期的女孩与高雄激素水平也表现出更大程度的 胰岛素抵抗与雄激素较低的肥胖女孩相比。该试点项目的目标1涉及详细的 评估青春期肥胖女孩的胰岛素抵抗和LH脉动性，其主要目标是 明确胰岛素抵抗在引起青春期肥胖女孩HA中的重要性。其次， 将评估LH升高在整个青春期肥胖相关HA中的贡献。表征 青春期前HA的潜在因素可能允许预测哪些青春期前和早期女孩将 随后出现PCOS症状。目标2的目标是调查可能 可能直接导致青春期女孩的HA，包括胰岛素样生长因子-I [IGF-I]，细胞因子， 和脂肪因子。在这种情况下，潜在的混杂因素（例如，胰岛素，LH）将被仔细评估。 该项目产生的数据将促使未来的U 54研究，以调查复杂的相互作用 导致PCOS的代谢和经典内分泌途径。

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.