Growth Hormone Activity in Polycystic Ovary Syndrome

描述(由申请人提供)：这项职业发展补助金将帮助候选人实现她的目标，成为一名独立资助的院士，致力于研究多囊卵巢综合征(PCOS)的病理生理学。人们对多囊卵巢综合征知之甚少，影响了5-8%的育龄妇女，导致不孕不育，并增加了糖尿病和心脏病的风险。这项建议的长期目标是提高对多囊卵巢综合征的病理生理学的了解，以便开发更有效的治疗方法。本申请中提出的新颖研究得益于一个强大的、多学科的高级研究团队的指导，并使用了一种新的生长激素拮抗剂作为生理探针。生长激素拮抗剂为分离生长激素在这种复杂且鲜为人知的疾病中的作用提供了第一个机会。这项建议的短期目标是确定生长激素和IGF-1在多囊卵巢综合征患者过度胰岛素抵抗和高雄激素血症中的作用。这项建议将首先在不太复杂的瘦型PCOS患者中调查这些影响，然后在更常见和更严重的肥胖PCOS患者中进行研究。这项建议的总体假设是，生长激素阻断将1)比正常人更大程度地降低患有多囊卵巢综合征的瘦弱女性的胰岛素抵抗；以及2)比对照女性更能减少患有多囊卵巢综合征的瘦弱女性的雄激素。与患有多囊卵巢综合征的苗条女性相比，这些影响在患有多囊卵巢综合征的肥胖女性中预计会放大。在所有组中，生长激素活性首先被阻断在次最大水平以维持正常的IGF-1水平，然后在高水平被阻断以导致IGF-1缺乏，以便区分生长激素和IGF-1在PCOS中的作用。除了指导研究，候选人还将接受肥胖症研究技术和生物统计学方面的高级培训，这将使她巩固自己在临床研究方面的基础。这一应用得益于内分泌学和生殖内分泌学分部和北卡罗来纳大学综合临床研究中心提供的强大的研究密集型环境和资源。受保护的指导研究时间和教学培训的结合是理想的，将使她发展经验、技能和初步数据，以发展为一名独立的临床医生-科学家。

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.