Regulation of drug-metabolizing cytochrome P450 enzymes by glucocorticoids

Drug Metab Rev. 2010 Nov;42(4):621-35. doi: 10.3109/03602532.2010.484462.


The regulation of drug-metabolizing cytochrome P450 enzymes (CYP) is a complex process involving multiple mechanisms. Among them, transcriptional regulation through ligand-activated nuclear receptors is the crucial mechanism involved in hormone-controlled and xenobiotic-induced expression of drug-metabolizing CYPs. In this article, we focus, in detail, on the role of the glucocorticoid receptor (GR) in the transcriptional regulation of human drug-metabolizing CYP enzymes and the mechanisms of the regulation. There are at least three distinct transcriptional mechanisms by which GR controls the expression of CYPs: 1) direct binding of GR to a specific gene-promoter sequence called the glucocorticoid responsive element (GRE); 2) indirect binding of GR in the form of a multiprotein complex to gene promoters without a direct contact between GR and promoter DNA; and 3) up- or downregulation of other CYP transcriptional regulators or nuclear receptors (i.e., transcriptional regulatory cross-talk). However, due to the general effect of glucocorticoids on numerous cellular pathways and functions, the net transcriptional effect of glucocorticoids on drug-metabolizing enzymes is usually a combination of several mechanisms. Since synthetic glucocorticoids are widely prescribed in human pharmacotherapy for the treatment of many diseases, comprehensive understanding of the transcriptional regulation of drug-metabolizing CYPs via GR with respect to glucocorticoid therapy or glucocorticoid hormonal status will aid in the development of efficient individualized pharmacotherapy without drug-drug interactions.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cytochrome P-450 Enzyme System / metabolism*
  • Cytochrome P-450 Enzyme System / physiology
  • Glucocorticoids / chemistry
  • Glucocorticoids / metabolism*
  • Humans
  • Pharmaceutical Preparations / metabolism*
  • Receptors, Glucocorticoid / physiology*


  • Glucocorticoids
  • Pharmaceutical Preparations
  • Receptors, Glucocorticoid
  • Cytochrome P-450 Enzyme System