Cortisol Metabolism & Central Adiposity After Menopause

描述（由申请人提供）：候选人：候选人，Wendolyn S. Gozansky，医学博士，公共卫生硕士，决心成为绝经期妇女健康领域的独立资助研究员。她的背景包括妇女研究的本科培训，流行病学研究的经验，以及内科和老年病学的临床培训。Gozansky博士获得了个人NRSA和Hartford/AFAR老年奖学金奖的支持，对老年妇女中央性脂肪组织积累机制进行了初步研究。比森职业发展奖将为她提供受保护的时间，让她获得在研究中应用基础科学概念所需的知识和技术技能，进行下面描述的研究，并在更年期内分泌学和代谢疾病预防方面建立一个独立的研究项目。环境：Gozansky博士所能获得的指导和机构资源是独一无二的。发起人Wendy M. Kohrt博士和共同发起人Robert S. Schwartz医学博士、Mark W. Geraci医学博士和Steven R. Smith医学博士将传授他们各自在雌激素、代谢和肥胖干预试验方面的专业知识，以及体内和体外糖皮质激素代谢评估的表现。她的赞助商GCRC的外部资助实验室和临床科学博士课程构成了Gozansky博士职业培训计划的关键基础设施。

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.