ER AND GR MEDIATED TRANSCRIPTIONAL REGULATION

1) The Applicant is in the fourth year of her Clinical Investigator Award (K08 DK02335-04). She is an Assistant Research Biochemist in the Metabolic Research Unit at UCSF currently spending 100 percent time in research activities. 2) Research Accomplishments: Under the K08 award, Dr. Uht has published a first authored paper and has co-authored several others. She was also selected to participate in the NSF sponsored Young Investigator Symposium in the 1996 Workshop on Steroid Hormones and Brain Function and invited to present at the 1998 American Neuroendocrine Society Workshop. She has authored several abstracts, presenting her work in poster form at national meetings. 3) Research Plan: Long Term Objectives: to elucidate the molecular mechanisms by which estrogens and glucocorticoids regulate physiologic and pathophysiologic states in the nervous system by combining molecular and in vivo approaches. SPECIFIC AIMS 1, 4, and to a large extent 2, of the original K08 have been accomplished. The current proposal is designed to expedite progress on the remaining Specific Aims. They are: Specific Aim 1: Generate mice transgenic for steroid receptor activated reporter genes. Specific Aim 2: Analyze mechanisms by which ER and GR mediate transcriptional regulation at certain AP-1 sites. Specific Aim 3: Establish a yeast system which will permit analysis of factors required for the ER/GR/AP-1 site interaction. 4) Environment/Career Development: The environment at UCSF remains rich and supportive. If granted, R03 will greatly facilitate the development of the reporter transgenic mice and the yeast system. The preliminary data obtained will be used to support an application for an R01. The R03 will also facilitate publishing manuscripts to report work currently in progress.