abstract / toc / Physiology / Master / Master of Philosophy

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The androgen receptor (AR) is a ligand-activated transcription factor and a member of the nuclear receptor superfamily. Mutations in the androgen receptor are associated with androgen insensitivity syndrome (AIS), and a neurodegenerative disease, spinal bulbar muscular atrophy (SBMA). Most of the mutations causing AIS are loss-of-function missense mutations whereas SBMA is caused by a gain-of-function polyglutamine expansion in the N-terminal domain of the protein. Characterization of AR mutations has led to a better understanding of structure-function relationships of the AR and serves as a prototype for steroid receptors mechanisms of action. / In the first paper, we examine the role of an AR mutation in causing mild androgen insensitivity syndrome. We found that this mutation conferred reduced transactivation by AR through impaired interactions with the AR coactivator, TIF2, and impaired homodimerization. / In the second paper, we investigate the role of the AR polyGln expansion mutation in SBMA pathogenesis. Recent evidence has implicated proteolytic degradation of polyGln-expanded proteins and their subsequent intracellular aggregation in polyGn-expanded disease pathogenesis. We examined the role and composition of aggregates using fluorescently-tagged AR and found that proteolysis need not be a prerequisite for aggregation and that aggregation is not necessary for poly-Gln-induced cellular toxicity. / Finally, we characterize the novel heterodimerization of AR and ERalpha. We determined that this direct interaction has functional implications for the transactivational properties of both receptors.

Thesis (M. Phil.)--University of Hong Kong, 2007. / Also available in print.

Thesis (M. Phil.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 76-85).

Thesis (Ph. D.)--Michigan State University. Dept. of Neuroscience, 2008. / Cindy Jordan, graduate advisor--From acknowledgments. Title from PDF t.p. (viewed Aug. 20, 2009). Includes bibliographical references (p. 139-155). Also issued in print.

Thesis (M.A.)--University of North Carolina at Chapel Hill, 2004. / Includes bibliographical references (leaves 76-79). Also available online (PDF file) by a subscription to the set or by purchasing the individual file.

Thesis (Ph. D.)--University of Wisconsin--Madison, 1969. / Typescript. Vita. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (M.A.)--University of North Carolina at Chapel Hill, 2004. / Includes bibliographical references (leaves 76-79).

Thesis (Ph. D.)--Ohio State University, 2007. / Title from first page of PDF file. Includes bibliographical references (p. 143-162).