Molecular mechanisms of glucocorticoid action and resistance.
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-kappa B. It has been shown that these mechanisms can significantly inhibit glucocorticoid signaling, and could therefore seriously decrease the efficacy of glucocorticoids used clinically.
Schaaf
Marcel J M
MJ
Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, 111 Alexander Drive, P.O. Box 12233, Research Triangle Park, NC 27709, USA.
Cidlowski
John A
JA
D021581:Active Transport, Cell Nucleus; D000818:Animals; D004247:DNA / Q000378:metabolism; D015536:Down-Regulation; D005938:Glucocorticoids / Q000378:metabolism*; D006801:Humans; D008024:Ligands; D008954:Models, Biological; D008957:Models, Genetic; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D011485:Protein Binding; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D011965:Receptors, Glucocorticoid / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation
D005938:Glucocorticoids; D008024:Ligands; D016328:NF-kappa B; D020033:Protein Isoforms; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D004247:DNA