ETIOLOGICAL FACTORS OF OBESITY-ASSOC HYPERANDROGENEMIA IN PERIPUBERTAL GIRLS

青春期前后女孩肥胖相关高雄激素血症的病因

• 批准号: 8167184
• 负责人: Christopher Rolland McCartney
• 金额: $ 4.01万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2013-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167184
• 关键词: Adolescent; Adult; Androgens; Blood specimen; Complex; Computer Retrieval of Information on Scientific Projects Database; Data; Development; Disease; Dyslipidemias; Endocrine; Estradiol; Exhibits; Feedback; Functional disorder; Funding; Future; Glucose Intolerance; Goals; Gonadotropin Hormone Releasing Hormone; Grant; Hypertension; Hypothalamic structure; Institution; Insulin; Insulin Resistance; Lead; Luteinizing Hormone; Metabolic; Neurosecretory Systems; Obesity; Pathway interactions; Physiologic pulse; Pilot Projects; Play; Polycystic Ovary Syndrome; Progesterone; Puberty; Relative (related person); Research; Research Personnel; Resistance; Resources; Role; Source; Symptoms; United States National Institutes of Health; Woman; girls; novel

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Polycystic ovary syndrome (PCOS) is a common disorder of women marked by hyperandrogenemia and ovulatory dysfunction. Additionally, PCOS is associated with obesity and a number of metabolic abnormalities including insulin resistance, glucose intolerance, dyslipidemia, and hypertension. A number of pathophysiological mechanisms underlie PCOS. Neuroendocrine abnormalities play a significant role in most women with PCOS, and PCOS is associated with relative resistance of the gonadotropin releasing hormone (GnRH) pulse generator to negative feedback by progesterone and estradiol. This hypothalamic resistance to negative feedback appears to be a result of hyperandrogenemia (HA), and can also occur in adolescents with HA. We have hypothesized that peripubertal HA-which can represent a forerunner of adult PCOS-can promote the development of PCOS in part via induction of hypothalamic resistance to negative feedback. However, the cause of peripubertal HA remains largely 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 androgen levels observed among obese girls-are unknown. We have gathered preliminary data that 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. The primary goal of this pilot project is to begin to establish the relationship between insulin resistance-as determined by insulin clamp studies-in causing HA in obese peripubertal girls. Secondarily, the investigators aim to assess the contributions of elevated luteinizing hormone-determined by frequent blood sampling for LH-in obesity-associated HA across puberty. 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. Data generated by this project will prompt novel future studies to investigate the complex interactions among metabolic and classical endocrine pathways that lead to PCOS.

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 多囊卵巢综合征(PCOS)是一种以高雄激素血症和排卵功能障碍为特征的女性常见疾病。此外，多囊卵巢综合征还与肥胖和一些代谢异常有关，包括胰岛素抵抗、糖耐量低减、血脂异常和高血压。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多囊卵巢综合征患者中起重要作用，多囊卵巢综合征与促性腺激素释放激素(GnRH)脉冲发生器对孕酮和雌二醇负反馈的相对抵抗有关。这种下丘脑对负反馈的抵抗似乎是高雄激素血症(HA)的结果，也可能发生在患有HA的青少年中。我们假设，青春期前后的HA--可以代表成人多囊卵巢综合征的先兆--可以部分地通过诱导下丘脑对负反馈的抵抗来促进多囊卵巢综合征的发展。然而，青春期HA的病因在很大程度上仍不清楚。肥胖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肥胖与HA有关。然而，青春期肥胖和透明质酸之间关系的潜在机制--以及肥胖女孩中观察到的雄激素水平的显著差异--尚不清楚。我们收集的初步数据表明，与雄激素水平较低的肥胖女孩相比，雄激素水平较高的青春期前和青春期早期肥胖女孩也表现出更大程度的胰岛素抵抗。这个试点项目的主要目标是开始确定胰岛素抵抗--由胰岛素钳研究确定--与导致肥胖青春期女孩HA之间的关系。其次，研究人员的目标是评估黄体生成素升高在青春期肥胖相关HA中的作用。黄体生成素是通过频繁采血检测黄体生成素确定的。表征青春期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随后会发展为多囊卵巢综合征的症状。该项目产生的数据将促使未来进行新的研究，以探索导致多囊卵巢综合征的代谢和经典内分泌途径之间的复杂相互作用。