Generalized and tissue specific glucocorticoid resistance

Mol Cell Endocrinol. 2021 Jun 15:530:111277. doi: 10.1016/j.mce.2021.111277. Epub 2021 Apr 14.

Abstract

Glucocorticoids (GCs) are steroid hormones that influence several physiologic functions and are among the most frequently prescribed drugs worldwide. Resistance to GCs has been observed in the context of the familial generalized GC resistance (Chrousos' syndrome) or tissue specific GC resistance in chronic inflammatory states. In this review, we have summarized the major factors that influence individual glucocorticoid sensitivity/resistance. The fine-tuning of GC action is determined in a tissue-specific fashion that includes the combination of different GC receptor promoters, translation initiation sites, splice isoforms, interacting proteins, post-translational modifications, and alternative mechanisms of signal transduction.

Keywords: Glucocorticoid receptor; Glucocorticoid resistance; Glucocorticoid signaling.

Publication types

  • Review

MeSH terms

  • Animals
  • Drug Resistance*
  • Glucocorticoids / pharmacology*
  • Humans
  • Organ Specificity
  • Promoter Regions, Genetic
  • Protein Processing, Post-Translational
  • RNA Splicing
  • Receptors, Glucocorticoid / genetics*
  • Receptors, Glucocorticoid / metabolism*
  • Signal Transduction / drug effects

Substances

  • Glucocorticoids
  • NR3C1 protein, human
  • Receptors, Glucocorticoid