Human Glucocorticoid Receptor Isoform Beta: Recent Understanding of Its Potential Implications in Physiology and Pathophysiology

Overview

Journal Cell Mol Life Sci

Publisher Springer

Specialty Biology

Date 2009 Jul 28

PMID 19633971

Citations 75

Authors

Tomoshige Kino

Yan A Su

George P Chrousos

Affiliations

Soon will be listed here.

Abstract

The human glucocorticoid receptor (GR) gene expresses two splicing isoforms alpha and beta through alternative use of specific exons 9alpha and 9beta. In contrast to the classic receptor GRalpha, which mediates most of the known actions of glucocorticoids, the functions of GRbeta have been largely unexplored. Owing to newly developed methods, for example microarrays and the jellyfish fluorescence proteins, we and others have recently revealed novel functions of GRbeta. Indeed, this enigmatic GR isoform influences positively and negatively the transcriptional activity of large subsets of genes, most of which are not responsive to glucocorticoids, in addition to its well-known dominant negative effect against GRalpha-mediated transcriptional activity. A recent report suggested that the "ligand-binding domain" of GRbeta is active, forming a functional ligand-binding pocket associated with the synthetic compound RU 486. In this review, we discuss the functions of GRbeta, its mechanisms of action, and its pathologic implications.

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