Glucocorticoids: Molecular mechanisms of action

Abstract

Since their discovery in the 1940s, glucocorticoids remain one of the most widely prescribed drugs in the world to treat inflammatory and autoimmune disorders, including arthritis, multiple sclerosis, asthma, ulcerative colitis, eczema, and psoriasis. They are also used as potent immunosuppressants after an organ transplant, and in the treatment of hematological cancers. Although the clinical value of glucocorticoids has been known for almost 80 years, the molecular mechanisms underlying their systemic and tissue-specific actions are still a subject of intense investigation. In this chapter, we provide an overview of the mechanisms regulating glucocorticoid synthesis, secretion, bioavailability, physiological effects, and their signaling via the glucocorticoid receptor (GR). We briefly review the gene and protein structure of the glucocorticoid receptor and its isoforms, as well as the glucocorticoid receptor genomic and non-genomic mechanisms of action. Finally, we discuss in detail the current knowledge of glucocorticoid effects on the regulation of the inflammatory response from a molecular perspective.