Project Summary

Rosalie M. Uht, M.D., Ph.D. (Young Investigator 2003) of University of Virginia, will examine the hypothalamic-pituitary-adrenal-axis (HPA axis), which is the system that mounts a person's response to stress (defined as any stimulus that elicits increased systemic levels of glucocorticoids).  Normally, activation of the HPA axis is negatively regulated by its end product, which is glucocorticoids.  However, depressed individuals cannot successfully mount this “down-regulation”.  As depressive illness occurs more frequently in women than men, it appears that estrogens regulate the HPA axis.  A gender difference in the stress response in rats actually supports this theory.  Dr. Uht will study an area in the brain where estrogen and glucocorticoid signal integration may interface-hypothalamic corticotropin-releasing hormone (CRH) neurons.  She hopes to elucidate how the CRH gene is regulated by Estrogen Receptors (ER), and how glucocorticoid receptors alter ER regulation.  This information may then be used to design selective estrogen receptor modulators that would specifically target estrogen's influence on the stress response in the brain.

Program Area: MOOD DISORDERS\Depression (Unipolar)

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