Journal
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY
Volume 83, Issue 1-5, Pages 37-48Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0960-0760(02)00263-7
Keywords
glucocorticoid; glucocorticoid receptor; homologous down-regulation; beta-isoform; NF-kappa B
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The actions of glucocorticoid hormones are mediated by an intracellular receptor, the glucocorticoid receptor (GR). The mechanism of action of this ligand-inducible transcription factor is discussed, focusing on mechanisms of glucocorticoid resistance. Three mechanisms are highlighted: ligand-induced down-regulation of the receptor, the dominant-negative inhibition by the beta-isoform of the receptor, and repression by the transcription factor NF-kappaB. It has been shown that these mechanisms can significantly inhibit glucocorticoid signaling, and could therefore seriously decrease the efficacy of glucocorticoids used clinically. (C) 2003 Published by Elsevier Science Ltd.
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