• Uht, Rosalie (PI)

Project Details


Long term objectives - To elucidate neuronal mechanisms of
estrogen and glucocorticoid receptor (ER & GR) transcriptional
regulation by combining molecular genetic and physiologic
approaches. SPECIFIC AIMS 1- To investigate the molecular
mechanisms which underlie an observed functional interaction
between the ER & GR at the AP-1 cis element (IRE). Specific Aim 1
: To establish the ER/GR/IRE interaction. Specific Aim 2: To
determine the effect of different Jun and Fos family members on
the interaction by transfection studies. Specific Aim 3: To
investigate molecular mechanisms of the interaction in mammalian
cells and yeast. SPECIFIC AIMS 4&5: To analyze mechanisms of ER
and GR transcriptional regulation through estrogen and
glucocorticoid response elements (ERE & GRE) and the IRE in vitro
and in vivo neuronal systems. Specific Aim 4: To analyze ER and
GR transcriptional regulation at ERE, GRE, and IRE in a neuronal
cell line. Specific Aim 5: To generate mice transgenic for ERE,
GRE and TRE activated reporter transgenes. Accomplishing these
specific aims will elucidate molecular mechanisms of the stress
response and effects of stress on reproductive function. Specific
Aims 1-3 will be accomplished by transfection studies in
mammalian cells and transformation of yeast. Yeast will provide a
highly efficient means for identifying protein surfaces required
for the ER/GR/TRE interaction. Specific Aims 4&5 will be
accomplished by constructing response element driven reporter
transgenes, testing them in the GT1 neuronal cell line, and
making transgenic mice. Steroid manipulations of mice will permit
identification of neurons and neuronal networks which contain
transcriptionally functional ER and GR.
Effective start/end date23/08/9531/07/01


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