The 11-ketosteroid 11-ketodexamethasone is a glucocorticoid receptor agonist

Mol Cell Endocrinol. 2004 Feb 12;214(1-2):27-37. doi: 10.1016/j.mce.2003.11.027.


Dexamethasone (Dex) is a potent and long-acting glucocorticoid in terms of anti-inflammatory activity without substantial sodium retaining effect. Here, we examine the ability of the 11beta-hydroxyglucocorticoids Dex and cortisol and their 11-keto forms 11-ketodexamethasone (11-ketoDex) and cortisone to bind to glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) and to mediate nuclear translocation and transactivation of a reporter-gene. Unlike cortisone, the 11-ketosteroid 11-ketoDex acts as a potent GR agonist, comparable to Dex and cortisol. Transactivation of MR by Dex or 11-ketoDex was weak or undetectable, despite efficient binding and induction of nuclear translocation. 11beta-HSD2 protects MR and GR from inappropriate occupation by cortisol; it is, however, unable to prevent activation of GR by 11-ketoDex. The finding that 11-ketoDex is a specific GR agonist may explain the potent glucocorticoid effect of Dex in tissues expressing 11beta-HSD2 including kidney and colon and also in certain tumor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Animals
  • Binding Sites
  • Cell Line
  • Dexamethasone / analogs & derivatives
  • Dexamethasone / pharmacology*
  • Humans
  • Hydrocortisone / pharmacology
  • Ketosteroids / pharmacology*
  • Kinetics
  • Protein Binding
  • Receptors, Glucocorticoid / agonists*
  • Receptors, Glucocorticoid / metabolism
  • Receptors, Glucocorticoid / physiology
  • Transcriptional Activation


  • 11-ketodexamethasone
  • Ketosteroids
  • Receptors, Glucocorticoid
  • Dexamethasone
  • Hydrocortisone