Glucocorticoid receptor: Implications for rheumatic diseases

Tomoshige Kino, E. Charmandari, G. P. Chrousos

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The glucocorticoid receptor (GR), a member of the nuclear receptor superfamily, mediates most of the known biologic effects of glucocorticoids. The human GR gene consists of 9 exons and expresses 2 alternative splicing isoforms, the GRa and GRβ. GRa is the classic receptor that binds to glucocorticoids and mediates most of the known actions of glucocorticoids, while GRβ does not bind to these hormones and exerts a dominant negative effect upon the GRα-induced transcriptional activity. Each of the two GR splice isoforms has 8 translational variants with specific transcriptional activity and tissue distribution. GRα consists of three subdomains, translocates from the cytoplasm into the nucleus upon binding to glucocorticoids, and regulates the transcriptional activity of numerous glucocorticoid-responsive genes either by binding to its cognate DNA sequences or by interacting with other transcription factors. In addition to these genomic actions, the GR also exerts rapid, non-genomic effects, which are possibly mediated by membranelocalised receptors or by translocation into the mitochondria. All these actions of the GR appear to play an important role in the regulation of the immune system. Specifically, the splicing variant GRβ may be involved in the pathogenesis of rheumatic diseases, while the circadian regulation of the GR activity via acetylation by the Clock transcription factor may have therapeutic implications for the preferential timing of glucocorticoid administration in autoimmune inflammatory disorders.

Original languageEnglish
JournalClinical and Experimental Rheumatology
Volume29
Issue number5 SUPPL. 68
Publication statusPublished - 2011
Externally publishedYes

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Keywords

  • Acetylation
  • Circadian rhythm
  • Glucocorticoid receptor
  • Non-genomic action
  • Splicing isoform
  • Transcriptional activity

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology

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