Cortisol Regulation in PCOS

多囊卵巢综合征中的皮质醇调节

• 批准号: 7035108
• 负责人: BETHANY J KLOPFENSTEIN
• 金额: $ 13.18万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-25 至 2011-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7035108
• 关键词: adipocytes; androgens; clinical research; cortisol; insulin sensitivity /resistance; metabolism; obesity

DESCRIPTION (provided by applicant): Project Summary Candidate: Bethany Klopfenstein, MD, is completing her fellowship in Endocrinology at Oregon Health & Science University (OHSU). This proposal will promote her scientific development and laboratory skills as she transitions into an independent academic, patient-oriented, clinical investigator. Her immediate career goals are to solidify her training in clinical research and develop new laboratory techniques for the study of cortisol metabolism. Her long-term goal is to develop an independent research career in the field of cortisol metabolism in insulin resistance. To accomplish these objectives, she will participate in a comprehensive didactic curriculum and perform the studies described in the research plan. Environment: OHSU has strong interdisciplinary training programs in both clinical and basic science research, including the Human Investigations Program funded by a K30 award. The 12,500 square foot OHSU General Clinical Research Center (GCRC) includes state-of-the-art outpatient and inpatient units, as well as a Core Laboratory, Bionutrition Unit, Bioinformatics Core and biostatistics support. Research Project: The overall goal of this research project is to investigate the relationships between cortisol metabolism, fat patterning, glucose metabolism, and adrenal androgens using the model of polycystic ovary syndrome (PCOS). Specific Aim 1 is a cross-sectional study designed to examine relationships between insulin sensitivity, central (visceral) obesity, androgen levels, and cortisol regulation (both at the systemic level of the hypothalamic-pituitary-adrenal (HPA) axis and locally in adipose tissue by the enzyme 11 betahydroxysteroid dehydrogenase type 1 (HSD 1) in women with PCOS and controls. Specific Aim 2 will prospectively test the novel hypothesis that insulin sensitizing agents improve body fat distribution and androgen levels in women with PCOS in part through reductions in HPA axis and adipocyte HSD 1 activity. Relevance: Individuals with central obesity, such as women with PCOS, are at high risk for developing infertility, diabetes, and heart disease. Abnormalities in cortisol metabolism may contribute to these comorbidities. Studies proposed here will improve our understanding of the regulation of cortisol metabolism, central obesity and insulin resistance. These findings may lead to new tools for managing PCOS.

描述（由申请人提供）： 项目摘要候选人：Bethany Klopfenstein，医学博士，即将在俄勒冈健康与科学大学 (OHSU) 完成内分泌学奖学金。随着她转变为独立的学术、以患者为导向的临床研究者，该提案将促进她的科学发展和实验室技能。她的近期职业目标是巩固临床研究方面的培训，并开发用于皮质醇代谢研究的新实验室技术。她的长期目标是在胰岛素抵抗的皮质醇代谢领域发展独立的研究事业。为了实现这些目标，她将参加综合教学课程并进行研究计划中描述的研究。环境：OHSU 在临床和基础科学研究方面拥有强大的跨学科培训项目，包括由 K30 奖项资助的人体研究项目。 12,500 平方英尺的 OHSU 普通临床研究中心 (GCRC) 包括最先进的门诊和住院单元，以及核心实验室、生物营养单元、生物信息学核心和生物统计支持。研究项目：该研究项目的总体目标是利用多囊卵巢综合征（PCOS）模型研究皮质醇代谢、脂肪模式、葡萄糖代谢和肾上腺雄激素之间的关系。具体目标 1 是一项横断面研究，旨在检查多囊卵巢综合征 (PCOS) 和多囊卵巢综合征 (PCOS) 女性的胰岛素敏感性、中枢性（内脏）肥胖、雄激素水平和皮质醇调节（在下丘脑 - 垂体 - 肾上腺 (HPA) 轴的系统水平和局部脂肪组织中 11 β 羟基类固醇脱氢酶 1 型 (HSD 1)）之间的关系。 控制。具体目标 2 将前瞻性地测试新假设，即胰岛素增敏剂部分通过减少 HPA 轴和脂肪细胞 HSD 1 活性来改善 PCOS 女性的体脂肪分布和雄激素水平。相关性：患有中心性肥胖的人，例如患有多囊卵巢综合症的女性，患不孕症、糖尿病和心脏病的风险很高。皮质醇代谢异常可能导致这些 合并症。这里提出的研究将提高我们对皮质醇代谢、中心性肥胖和胰岛素抵抗调节的理解。这些发现可能会带来治疗多囊卵巢综合症的新工具。