Cortisol Metabolism & Central Adiposity After Menopause

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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.