Corticosteroids: Mechanisms of Action in Health and Disease

Rheum Dis Clin North Am. 2016 Feb;42(1):15-31, vii. doi: 10.1016/j.rdc.2015.08.002.


Glucocorticoids are primary stress hormones that regulate a variety of physiologic processes and are essential for life. The actions of glucocorticoids are predominantly mediated through the classic glucocorticoid receptor (GR). GRs are expressed throughout the body, but there is considerable heterogeneity in glucocorticoid sensitivity and biologic responses across tissues. The conventional belief that glucocorticoids act through a single GR protein has changed dramatically with the discovery of a diverse collection of receptor isoforms. This article provides an overview of the molecular mechanisms that regulate glucocorticoid actions, highlights the dynamic nature of hormone signaling, and discusses the molecular properties of the GR isoforms.

Keywords: Glucocorticoid; Glucocorticoid receptor; Glucocorticoid signaling; Hypothalamic-pituitary-adrenal axis; Isoforms; Phosphorylation; Polymorphism.

Publication types

  • Research Support, N.I.H., Intramural
  • Review

MeSH terms

  • Adrenal Cortex Hormones / pharmacology
  • Gene Expression Regulation / drug effects
  • Glucocorticoids / pharmacology*
  • Humans
  • Hypothalamo-Hypophyseal System / drug effects*
  • Hypothalamo-Hypophyseal System / metabolism
  • Pituitary-Adrenal System / drug effects*
  • Pituitary-Adrenal System / metabolism
  • Polymorphism, Genetic
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein Processing, Post-Translational
  • Receptors, Glucocorticoid / drug effects*
  • Receptors, Glucocorticoid / genetics
  • Receptors, Glucocorticoid / metabolism
  • Signal Transduction


  • Adrenal Cortex Hormones
  • Glucocorticoids
  • Protein Isoforms
  • Receptors, Glucocorticoid