CAREER:Relevance of non-genomic estrogen signaling to neuromorphology and aggressive behavior

Tulane University, New Orleans LA

Investigators

Abstract

Estrogen, a steroid hormone is important for reproduction, social behaviors, cognition and the progression of several diseases such as breast and ovarian cancers. It influences these processes by binding a specific receptor, the estrogen receptor (ER) alpha or the ER beta. Traditionally, these receptors reside within cells and signal by slowly regulating the transcription of target genes. However, estrogen can also rapidly activate kinases and increase calcium within cells via putative receptors on the cell membrane. Dr. Vasudevan has previously demonstrated that estrogen, acting rapidly at the cell membrane can couple to increased transcription in the nucleus. This suggests that a novel integrated signaling pathway linking rapid cell membrane-initiated signaling to nuclear transcription is driven by estrogen in neurons. This project will elucidate various components of this signaling pathway; starting with the idea that coupling occurs via ER alpha phosphorylation. The importance of modification of the ER alpha that directly impacts ER alphafunction will be examined. Lastly, the importance of this pathway in known estrogen-mediated changes in aggressive behavior and neuromorphology will also be examined. Molecular biological approaches using ER in cell culture, and histochemical and behavioral analysis in animal models will be used to understand the significance of coupled-signaling. Understanding this pathway in the framework of biological function will close a critical gap in our understanding of this controversial mode of estrogen signaling and introduce a new paradigm in steroid receptor biology, applicable to any hormone responsive tissue. The activities in this project provide research opportunities not only for graduate students, but also for K-12 students and undergraduates, particularly those from minority and under-represented groups. In addition, undergraduates and graduates will gain exposure and global experience in international collaborations, scientific meetings and by authoring research publications.