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Genomic and nongenomic effects of glucocorticoids

Nature Clinical Practice Rheumatology volume 4, pages 525–533 (2008)Cite this article

Abstract

The strong anti-inflammatory and immunosuppressive effects of glucocorticoids are mediated primarily by the cytosolic glucocorticoid receptors. These receptors are members of the steroid hormone receptor family, a superfamily of ligand-inducible transcription factors, and exert genomic effects that can result in increased expression of regulatory—including anti-inflammatory—proteins (transactivation), or decreased production of proinflammatory proteins (transrepression). Transactivation is thought to be responsible for numerous adverse effects of glucocorticoids; transrepression is thought to be responsible for many of the clinically desirable anti-inflammatory and immunosuppressive effects of glucocorticoids. Optimized glucocorticoids, such as selective glucocorticoid receptor agonists, are being developed to try to minimize the adverse effects many patients experience. Glucocorticoids also exert their effects via rapid, nongenomic mechanisms that can be classified as involving nonspecific interactions of glucocorticoids with cellular membranes, nongenomic effects that are mediated by cytosolic glucocorticoid receptors, or specific interactions with membrane-bound glucocorticoid receptors. Increased understanding of these mechanisms of glucocorticoid action could enable the development of novel drugs with which to treat patients with inflammatory and autoimmune disease.

Key Points

  • Glucocorticoids are powerful and cost-effective drugs for the treatment of various rheumatic diseases

  • Several adverse effects limit the successful therapeutic use of glucocorticoids, especially if used at high doses for long periods of time

  • The strong anti-inflammatory and immunosuppressive effects are mediated by genomic and nongenomic mechanisms of action

  • A greater understanding of the detailed mechanisms of glucocorticoid action is required to improve the benefit:risk ratio of glucocorticoid therapy

  • Current intensive research focuses on the optimization of conventional glucocorticoid use (for drugs that are already available) and on the development of novel glucocorticoid receptor ligands

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Figure 1: One gene encodes different receptor variants.
Figure 2: Genomic effects of glucocorticoids include transactivation and transrepression.

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Author information

Authors and Affiliations

  1. C Stahn is Research Associate and F Buttgereit is Professor of Rheumatology at the Department of Rheumatology and Clinical Immunology, Charité University Hospital, Berlin, Germany.,

    Cindy Stahn & Frank Buttgereit

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  1. Cindy Stahn
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  2. Frank Buttgereit
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Correspondence to Frank Buttgereit.

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Competing interests

F Buttgereit has declared that he has been a consultant for, and received speakers bureau and grant/research support from, Merck Pharma GmbH and NiTech Pharma GmbH. F Buttgereit has also been a consultant for Organon. C Stahn declared no competing interests.

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Stahn, C., Buttgereit, F. Genomic and nongenomic effects of glucocorticoids. Nat Rev Rheumatol 4, 525–533 (2008). https://doi.org/10.1038/ncprheum0898

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