This action is to award funds for a Presidential Young Investigator. Dr. Robert Sapolsky has already embarked on a brilliant career in neuroendocrinology research. His work focuses on three basic questions: 1) What are the neuroendocrine abnormalities that underly syndromes of glucocorticoid hypersecretion; 2) What are the consequences of excessive exposure to glucocorticoids, in particular, what role do glucocorticoids play in mediating neuron death during aging and following neuropathologic insults; and 3) What are the cellular mechanisms by which glucocorticoids are neurotoxic? Dr. Sapolsky has already studied negative-feedback regulation of glucocorticoid secretion, focusing on the role of the hippocampus as an inhibitory negative-feedback brake upon adrenocorticoid activity, its role in terminating glucocorticoid secretion at the end of stress and the failure of this type of regulation in aged rats. He has refined and originated methods for quantitative measures for steroid receptors in the brain in order to examine the relationship between occupancy of hippocampal glucocorticoid receptors and the initiation of inhibitory hippocampal signals to the hypothalamus.