The Biology of the Glucocorticoid Receptor: New Signaling Mechanisms in Health and Disease

By R. Oakley, J. Cidlowski. Journal of Allergy and Clinical Immunology, 2013

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Glucocorticoids are primary stress hormones necessary for life that regulate numerous physiological processes in an effort to maintain homeostasis. Synthetic derivatives of these hormones have been mainstays in the clinic for treating inflammatory diseases, autoimmune disorders, and hematological cancers. The physiological and pharmacological actions of glucocorticoids are mediated by the glucocorticoid receptor (GR), a member of the nuclear receptor superfamily of ligand-dependent transcription factors. Ligand-occupied GR induces or represses the transcription of thousands of genes by direct binding to DNA response elements and/or by physically associating with other transcription factors. The traditional view that glucocorticoids act through a single GR protein has changed dramatically with the discovery of a large cohort of receptor isoforms with unique expression, gene-regulatory, and functional profiles. These GR subtypes are derived from a single gene by alternative splicing and alternative translation initiation mechanisms. Post-translational modification of these GR isoforms further expands the diversity of glucocorticoid responses. Here, we discuss the origin and molecular properties of the GR isoforms and their contribution to the specificity and sensitivity of glucocorticoid signaling in healthy and diseased tissues.

Subfields: Endocrinology, Diabetes and Metabolism, Genetics, Oncology

View Paper: https://www.semanticscholar.org/paper/03273e0c6e0564abba6ff2f2ed6c7b508e996ffb