Elizabeth M. Wilson, PhD
Professor of Pediatrics and Biochemistry and Biophysics
3340C Medical Biomolecular Research Building - Office
3330 - 3332 Medical Biomolecular Research Building - Lab
CB# 7500


Androgen Regulation of Gene Expression

Steroid hormone receptors are ligand activated transcription factors that regulate gene expression by binding specific DNA sequences and interacting with transcriptional regulatory proteins. We study the androgen receptor, a steroid receptor that mediates the effects of the biologically active androgens, testosterone and dihydrotestosterone. The goal of our studies is to elucidate the molecular mechanisms of androgen receptor action. We use a variety of techniques to establish structure-function relationships of the ligand binding, DNA binding, and transcriptional activation domains of the androgen receptor. The a-helical FXXLF and WXXLF motifs in the AR NH2-terminal region were found to mediate an androgen dependent interaction with activation function 2 in the carboxyl-terminal ligand binding domain that is necessary for the activation of many androgen dependent gene promoter/enhancers. Naturally occurring mutations in the human androgen receptor gene cause partial or complete androgen insensitivity that results in 46XY genetic males with a range of external genital phenotypes from normal appearing male to female. We study the functional effects of these mutations on androgen receptor transcriptional activity and are presently using yeast two hybrid screening methods to identify coactivator and corepressor proteins that interact with the androgen receptor to modulate gene expression. In collaborative studies, we investigate the activity of naturally occurring and synthetic compounds for androgen or antiandrogen activity that could act as endocrine disruptors of male sexual development.


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The Laboratories for Reproductive Biology
CB #7500
3340 Medical Biomolecular Research Building
111 Mason Farm Road
University of North Carolina - Chapel Hill, NC 27599
lrb@med.unc.edu - FAX: 919-966-2203

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