Cortisol Metabolism & Central Adiposity After Menopause

描述（由申请人提供）：候选人：候选人，温多琳S。Gozansky，医学博士，公共卫生硕士，决心成为一个独立资助的研究人员在更年期妇女的健康领域。她的背景包括妇女研究的本科培训，流行病学研究的经验，以及内科和老年医学的临床培训。Gozansky博士得到了NRSA个人和Hartford/AFAR老年病研究金的支持，对老年妇女中央脂肪组织积累的机制进行了试点研究。Beeson职业发展奖将提供受保护的时间，以获得在她的研究中应用基本科学概念所需的知识和技术技能，进行下述研究，并建立更年期内分泌学和代谢疾病预防的独立研究计划。环境：Gozansky博士可获得的指导和机构资源是特殊的。温迪·M赞助商Kohrt博士和Robert S. Schwartz，MD，Mark W. Geraci，MD和Steven R.共同发起人Smith博士将在雌激素、代谢和肥胖的干预试验以及糖皮质激素代谢的体内和体外评估方面传授各自的专业知识。她的赞助商GCRC的壁外资助实验室和临床科学博士项目构成了Gozansky博士职业培训计划的关键基础设施。 调研：绝经期会引发中心性肥胖的增加，这与高脂血症、高血压、心血管疾病和糖尿病密切相关。雌激素减少腹部脂肪堆积，但其机制尚不清楚。我们研究的工作模型是基于这样一个假设：绝经后雌激素缺乏会增加皮质醇向皮质醇的外周转化。我们认为，糖皮质激素代谢的失调引发了不成比例的中心性肥胖的积累。我们将确定雌二醇是否在外周组织中起作用，以减少可的松向皮质醇的净转化。生理学研究，如所提出的，是至关重要的，以指导新的预防性治疗，如选择性雌激素受体调节剂，最大限度地提高与雌激素相关的利益，同时最大限度地减少风险的发展。

DESCRIPTION (provided by applicant): Candidate: The candidate, Wendolyn S. Gozansky, MD, MPH, is determined to become an independently funded researcher in the area of menopausal women's health. Her background includes undergraduate training in women's studies, experience in epidemioiogic research, and clinical training in internal medicine and geriatrics. Dr. Gozansky was supported by an individual NRSA and a Hartford/AFAR Geriatric Fellowship Award to conduct a pilot study of mechanisms of central adipose tissue accumulation in older women. The Beeson Career Development Award will provide the protected time to acquire the knowledge and technical skills needed to apply basic science concepts in her research, to conduct the studies described below, and to build an independent research program in menopausal endocrinology and metabolic disease prevention. Environment: The mentorship and institutional resources available to Dr. Gozansky are exceptional. Wendy M. Kohrt, PhD, the sponsor, and Robert S. Schwartz, MD, Mark W. Geraci, MD, and Steven R. Smith, MD, the co-sponsors, will impart their respective expertise in intervention trials of estrogens, metabolism and adiposity, and the performance of in vivo and in vitro assessments of glucocorticoid metabolism. The extramurally funded laboratories of her sponsors, the GCRC, and the Doctoral Program in Clinical Sciences form the key infrastructure for Dr. Gozansky's career training plan. Research: The menopause triggers an increase in central adiposity, which is strongly linked to hyperlipidemia, hypertension, cardiovascular disease, and diabetes. Estrogens attenuate abdominal fat accumulation, but the mechanisms remain unknown. The working model for our studies centers on the hypothesis that estrogen deficiency after menopause increases peripheral conversion of cortisone to cortisol. We contend that this dysregulation of glucocorticoid metabolism triggers a disproportionate accumulation of central adiposity. We will determine whether estradiol acts in peripheral tissues to decrease the net conversion of cortisone to cortisol. Physiologic studies, such as the ones proposed, are critical to guide development of new preventive therapies, such as selective estrogen receptor modulators, that maximize benefits associated with estrogens while minimizing risks.