PILOT PROJECT - FACTORS DETERMINING OBESITY-ASSOCIATED HYPERANDROGENEMIA IN GIRLS

试点项目 - 女孩肥胖相关高雄激素血症的决定因素

• 批准号: 8239999
• 负责人: Christopher Rolland McCartney
• 金额: $ 15.87万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8239999
• 关键词: Adolescence; Adolescent; Adult; Androgens; Clinical; Complex; Data; Defect; Development; Disease; Endocrine; Estradiol; Exhibits; Feedback; Functional disorder; Future; Goals; Gonadotropin Hormone Releasing Hormone; Hypothalamic structure; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Lead; Luteinizing Hormone; Metabolic; Neurosecretory Systems; Obesity; Ovarian; Pathway interactions; Physiologic pulse; Pilot Projects; Play; Polycystic Ovary Syndrome; Population; Progesterone; Puberty; Relative (related person); Resistance; Role; Somatomedins; Symptoms; Syndrome; Testing; Woman; adipokines; cohort; cytokine; girls; novel; reproductive; Adolescence; Adolescent; Adult; Androgens; Clinical; Complex; Data; Defect; Development; Disease; Endocrine; Estradiol; Exhibits; Feedback; Functional disorder; Future; Goals; Gonadotropin Hormone Releasing Hormone; Hypothalamic structure; Insulin; Insulin Resistance; Insulin-Like Growth Factor I; Lead; Luteinizing Hormone; Metabolic; Neurosecretory Systems; Obesity; Ovarian; Pathway interactions; Physiologic pulse; Pilot Projects; Play; Polycystic Ovary Syndrome; Population; Progesterone; Puberty; Relative (related person); Resistance; Role; Somatomedins; Symptoms; Syndrome; Testing; Woman; adipokines; cohort; cytokine; girls; novel; reproductive

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.

多囊卵巢综合征（PCOS）是一种以高狂异生血症（HA）为标志的女性的常见疾病 和排卵功能障碍。此外，PCOS与肥胖和其他代谢异常有关 （例如胰岛素抵抗）。多种病理生理机制是PCOS的基础。神经内分泌 异常在大多数患有PCO的女性中起着重要作用。 PCOS与相对电阻有关 促性腺激素释放马龙脉冲发生器对孕酮和雌二醇的负反馈： 该缺陷似乎是HA的结果，也可以在HA的青少年中发生。我们已经假设了 peripubertal ha可以部分通过诱导下丘脑抗性来促进PCOS的发展 负面反馈。但是，杂伯伯伯伯伯伯伯伯伯伯伯的原因仍然未知。肥胖是一种公认​​的 成人PCOS HA的病理生理因素；最近的数据表明，周围肥胖是 与HA相关。但是，周围肥胖与 肥胖女孩中观察到的雄激素的明显变异性是未知的。初步数据 表明肥胖的雄激素水平高的青春期前和早期的青春期女孩也表现出更高的程度 与具有较低雄激素的肥胖女孩相比，胰岛素抵抗。该试点项目的目标1涉及详细 评估肥胖的女孩中胰岛素抵抗和LH搏动性的评估，其主要目标是 确定胰岛素抵抗在肥胖的伯里伯氏症女孩中引起HA的重要性。次要， 将评估与肥胖相关的HA在整个青春期中的LH升高的贡献。表征 杂伯伯伯伯伯伯伯伯的基础因素可能允许预测，前青春期前和早期的女孩将 随后，继续发展PCOS的症状。目标2的目标是调查其他可能的因素 合理地直接为HA中的HA贡献，包括胰岛素样生长因子-L [IGF-I]，细胞因子， 和脂肪因子。在这种情况下，将仔细评估潜在的混杂因素（例如胰岛素，LH）。 该项目生成的数据将促使新的未来U54研究来研究复杂的相互作用 在导致PCOS的代谢和经典内分泌途径中。