Molecular mechanisms of glucocorticoid action and resistance

J Steroid Biochem Mol Biol. 2002 Dec;83(1-5):37-48. doi: 10.1016/s0960-0760(02)00263-7.


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.

Publication types

  • Review

MeSH terms

  • Active Transport, Cell Nucleus
  • Animals
  • DNA / metabolism
  • Down-Regulation*
  • Glucocorticoids / metabolism*
  • Humans
  • Ligands
  • Models, Biological
  • Models, Genetic
  • NF-kappa B / metabolism
  • Phosphorylation
  • Protein Binding
  • Protein Isoforms
  • RNA, Messenger / metabolism
  • Receptors, Glucocorticoid / chemistry*
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / physiology*
  • Transcriptional Activation


  • Glucocorticoids
  • Ligands
  • NF-kappa B
  • Protein Isoforms
  • RNA, Messenger
  • Receptors, Glucocorticoid
  • DNA