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The Roles of Androgen Receptors and Androgen-Binding Proteins in Nongenomic Androgen Actions

George Whipple Laboratory for Cancer Research, Departments of Pathology (C.A.H., C.C.) and Urology (C.C.), University of Rochester, Rochester, New York 14642

Address all correspondence and requests for reprints to: Dr. Chawnshang Chang, George Whipple Laboratory for Cancer Research, University of Rochester, Department of Pathology, Box 626, 601 Elmwood Avenue, Rochester, New York 14642. E-mail: chang{at}urmc.rochester.edu.

ABSTRACT

The biological activity of testosterone and dihydrotestosterone is thought to occur predominantly through binding to the androgen receptor (AR), a member of the nuclear receptor superfamily that functions as a ligand-activated transcription factor. However, androgens have also been reported to induce the rapid activation of kinase-signaling cascades and modulate intracellular calcium levels. These effects are considered to be nongenomic because they occur in cell types that lack a functional AR, in the presence of inhibitors of transcription and translation, or are observed to occur too rapidly to involve changes in gene transcription. Such nongenomic effects of androgens may occur through AR functioning in the cytoplasm to induce the MAPK signal cascade. In addition, androgens may function through the sex hormone binding globulin receptor and possibly a distinct G protein-coupled receptor to activate second messenger signaling mechanisms. The physiological effect of nongenomic androgen action has yet to be determined. However, it may ultimately contribute to regulation of transcription factor activity, including mediation of the transcriptional activity of AR.

NURSA Molecule Pages Link:

Nuclear Receptors:   AR

Coregulators:   SRC-1

Ligands:   Dihydrotestosterone  |  R1881

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