Molecular regulation of estrogen receptor gene expression in the adult

With support from the National Science Foundation, I will conduct a three-year study investigating the molecular mechanisms by which critical genes are regulated in the rodent brain. The gene of interest in the current study is estrogen receptor-alpha. Estradiol exposure during development is critical for establishing long-term structural and functional aspects of the brain as well as modulating neural responses in the adult brain. Estradiol acts through intracellular receptors that mediate its action. Estrogen receptor gene expression is developmentally regulated and this proposal will explore the novel molecular mechanisms of this regulation in the adult brain in a sex-specific manner. In particular, the effects of epigenetic modification of DNA by methylation will be examined in a mouse animal model. Techniques such as in situ hybridization, real-time polymerase chain reaction and chromatin immunoprecipitation will be employed. The overall intellectual merit of this proposal will be derived from our enhanced understanding of the regulation of gene expression in the brain in the adult which can lead to altered responses to brain injury in a sex-specific manner. This proposal combines the fields of neuroendocrinology with the rapidly growing field of epigenetics. This is a new and unique area of investigation. Furthermore, the study of sex differences is a topic of interest for the NSF as demonstrated by the support of the recent Organization for Study of Sex Differences annual meeting in Ann Arbor, MI by NSF.