Martin J. Kelly IBN-9500239 Steroid hormones play central roles in many bodily functions including neural development, reproduction, salt and water homeostasis, response to environmental stressors, skeletal maintenance and grmwth, and blood pressure to mention a few. It is generally agreed that the actions of these powerful hormones are exerted by binding to intracellular receptors which subsequently dimerize and bind to nuclear DNA where they act to facilitate or inhibit gene transcription. These actions usually take hours to days to be manifested. However, several electrophysiological and behavioral studies have reported very rapid effects of these hormones, in the seconds to minutes time frame. The rapid action of the hormones suggest that a nuclear site of action is highly unlikely and is more consistent with the existence of membrane bound G-protein-coupled receptors. Dr. Kelly has assembled a team of skilled investigators, experienced in molecular biology, behavior and electrophysiology to isolate and clone these novel steroid receptors for estrogen and glucocorticoid hormones. Using the latest in expression cloning strategies, this group proposes to isolate and characterize G-protein coupled receptors for glucocorticoids and estrogen, to study the physiological role of these novel receptors in cellular metabolism, to identify their natural ligands and begin to design agonists and antagonists for future study. This proposal is appropriate for a SGER award because these studies are novel and highly exciting. Moreover, if successful, the outcome will revolutionize our understanding of the mechanism of steroid hormones action and have major impacts in the fields of neuroscience, endocrinology and behavior.
