Cortisol Metabolism & Central Adiposity After Menopause

候选人：候选人温多琳·S·戈赞斯基，医学博士，公共卫生硕士，决心成为一名在更年期妇女健康领域独立资助的研究人员。她的背景包括女性研究的本科培训，流行病学研究的经验，以及内科和老年病学的临床培训。戈赞斯基博士得到了个人NRSA和哈特福德/阿法尔老年研究奖学金奖的支持，对老年女性中心脂肪组织积累的机制进行了初步研究。比森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，进行下文所述的研究，并建立更年期内分泌学和代谢性疾病预防方面的独立研究计划。环境：戈赞斯基博士可以得到的指导和机构资源是出类拔萃的。发起人温迪·M·科尔特博士和共同发起人罗伯特·S·施瓦茨医学博士、马克·W·格拉奇医学博士和史蒂文·R·史密斯医学博士将在雌激素、新陈代谢和肥胖症的干预试验以及糖皮质激素代谢的体内和体外评估方面提供各自的专业知识。她的赞助商GCRC的外部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。 研究：更年期会引发中心性肥胖症的增加，这与高脂血症、高血压、心血管疾病和糖尿病密切相关。雌激素可以减少腹部脂肪堆积，但其机制尚不清楚。我们研究的工作模型以这样一种假设为中心，即绝经后雌激素缺乏会增加外周皮质醇向皮质醇的转化。我们认为，糖皮质激素代谢的这种失调触发了中心性肥胖的不成比例的积累。我们将确定雌激素是否在外周组织中起作用，以减少皮质醇向皮质醇的净转化。生理学研究，如所提出的，对于指导新的预防性治疗的发展至关重要，例如选择性雌激素受体调节剂，在最大限度地增加与雌激素相关的好处的同时将风险降至最低。

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.