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Cellular and Molecular Life Sciences

, Volume 66, Issue 21, pp 3435–3448 | Cite as

Human glucocorticoid receptor isoform β: recent understanding of its potential implications in physiology and pathophysiology

  • Tomoshige KinoEmail author
  • Yan A. Su
  • George P. Chrousos
Review

Abstract

The human glucocorticoid receptor (GR) gene expresses two splicing isoforms α and β through alternative use of specific exons 9α and 9β. In contrast to the classic receptor GRα, which mediates most of the known actions of glucocorticoids, the functions of GRβ 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 GRβ. 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 GRα-mediated transcriptional activity. A recent report suggested that the “ligand-binding domain” of GRβ is active, forming a functional ligand-binding pocket associated with the synthetic compound RU 486. In this review, we discuss the functions of GRβ, its mechanisms of action, and its pathologic implications.

Keywords

Cytoplasmic to nuclear translocation Glucocorticoid receptor Ligand-binding pocket Microarray Splicing isoform Zebrafish 

Notes

Acknowledgment

Literary work of this article was funded partly by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD.

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Copyright information

© US Government 2009

Authors and Affiliations

  • Tomoshige Kino
    • 1
    Email author
  • Yan A. Su
    • 2
  • George P. Chrousos
    • 3
  1. 1.Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human DevelopmentNational Institutes of HealthBethesdaUSA
  2. 2.GenProMarkers, Inc.RockvilleUSA
  3. 3.First Department of PediatricsAthens UniversityAthensGreece

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