Growth Hormone Activity in Polycystic Ovary Syndrome

多囊卵巢综合症中的生长激素活性

• 批准号: 7136390
• 负责人: JULIE LUND SHARPLESS
• 金额: $ 15.91万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-07 至 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7136390
• 关键词: androgens; blood chemistry; body physical characteristic; clinical research; female; glucose tolerance test; hormone inhibitor; hormone regulation /control mechanism; human subject; insulin sensitivity /resistance; insulinlike growth factor; mentoring /mentor; obesity; pathologic process; patient oriented research; photon absorptiometry; pituitary disorders; polycystic ovary syndrome; secretion; somatotropin; women' s health

DESCRIPTION (provided by applicant): This career development grant will prepare the candidate to pursue her goal of becoming an independently funded academician devoted to investigating the pathophysiology of Polycystic Ovary Syndrome (PCOS). The poorly understood syndrome of PCOS affects 5-8% of reproductive age women and results in infertility as well as an increased risk of diabetes and heart disease. The long term objective of this proposal is to improve understanding of the pathophysiology of PCOS in order that more effective treatments can be developed. The novel research proposed in this application benefits from mentoring by a strong, multidisciplinary team of senior investigators and uses a new growth hormone antagonist as a physiological probe. The growth hormone antagonist offers the first opportunity to isolate the effects of growth hormone in this complex and poorly understood disease. The short term goal of this proposal is to determine the contribution of growth hormone and IGF-1 to the excess insulin resistance and hyperandrogenism in PCOS. This proposal will investigate these effects first in the less complex lean PCOS patients and then in the more common and more severe obese PCOS patients. The overall hypotheses of this proposal are that growth hormone blockade will 1) decrease insulin resistance in lean women with PCOSto a greater extent than in normals; and 2) decrease androgens in lean women with PCOS more than in control women. These effects are expected to be magnified in obese women with PCOS in comparison to lean women with PCOS. In all groups growth hormone activity will first be blocked at a submaximal level to preserve normal IGF-1 levels, and then at a high level to induce IGF-1 deficiency in order to distinguish between the roles of growth hormone and IGF-1 in PCOS. In addition to the mentored research, the candidate will undertake advanced training in obesity research techniques and biostatistics that will allow her to solidify her foundation in clinical research. This application benefits from the robust, research-intensive environment and resources provided by the Divisions of Endocrinology and Reproductive Endocrinology and the General Clinical Research Center at UNC. The combination of protected time for mentored research and didactic training are ideal and will allow her to develop the experience, skills and preliminary data to develop as an independent clinician- scientist.

描述（由申请人提供）：这项职业发展赠款将为候选人做好准备，以实现她成为一名专门研究多囊卵巢综合征（PCOS）病理生理学的独立资助的院士的目标。 PCOS的综合征鲜为人知的综合征会影响5-8％的生殖年龄妇女，导致不孕症以及糖尿病和心脏病的风险增加。该建议的长期目标是提高对PCOS病理生理学的理解，以便可以开发出更有效的治疗方法。该应用程序中提出的新研究受益于由高级研究人员组成的强大，多学科团队的指导，并使用新的生长激素拮抗剂作为生理探针。生长激素拮抗剂提供了第一个机会，可以隔离生长激素在这种复杂且理解不足的疾病中的影响。该提案的短期目标是确定生长激素和IGF-1对PCOS中过量胰岛素抵抗和超雄激素的贡献。该提案将首先在不太复杂的瘦PCOS患者中，然后在更常见，更严重的肥胖PCOS患者中研究这些影响。该提议的总体假设是生长激素阻滞将使PCOSTO患有PCOSTO的瘦女性的胰岛素抵抗降低的程度要大于正常妇女的胰岛素耐药性； 2）与对照女性相比，具有PCOS的瘦女性的雄激素减少。与患有PCOS的瘦女性相比，肥胖女性有望在肥胖女性中放大这些作用。在所有组中，生长激素活性将首先在次最大水平上阻塞，以保持正常的IGF-1水平，然后在高水平上诱导IGF-1缺乏症，以区分PCOS生长激素和IGF-1的作用。除了指导研究外，候选人还将接受肥胖研究技术和生物统计学的高级培训，这将使她能够巩固自己的临床研究基础。该应用程序受益于内分泌和生殖内分泌学和UNC的一般临床研究中心提供的强大，研究密集型环境和资源。受到指导研究和教学培训的受保护时间的结合是理想的选择，将使她能够发展经验，技能和初步数据，以发展为独立的临床医生 - 科学家。