Glucocorticoid sensitivity in health and disease

Rogier Quax, Laura Manenschijn, Frans Koper, Mieke Hazes, S.W.J. Lamberts, Liesbeth van Rossum, R.A. Feelders

Research output: Contribution to journalArticleAcademicpeer-review

189 Citations (Scopus)

Abstract

Glucocorticoids regulate many physiological processes and have an essential role in the systemic response to stress. For example, gene transcription is modulated by the glucocorticoid-glucocorticoid receptor complex via several mechanisms. The ultimate biologic responses to glucocorticoids are determined by not only the concentration of glucocorticoids but also the differences between individuals in glucocorticoid sensitivity, which is influenced by multiple factors. Differences in sensitivity to glucocorticoids in healthy individuals are partly genetically determined by functional polymorphisms of the gene that encodes the glucocorticoid receptor. Hereditary syndromes have also been identified that are associated with increased and decreased sensitivity to glucocorticoids. As a result of their anti-inflammatory properties, glucocorticoids are widely used in the treatment of allergic, inflammatory and haematological disorders. The variety in clinical responses to treatment with glucocorticoids reflects the considerable variation in glucocorticoid sensitivity between individuals. In immune-mediated disorders, proinflammatory cytokines can induce localized resistance to glucocorticoids via several mechanisms. Individual differences in how tissues respond to glucocorticoids might also be involved in the predisposition for and pathogenesis of the metabolic syndrome and mood disorders. In this Review, we summarize the mechanisms that influence glucocorticoid sensitivity in health and disease and discuss possible strategies to modulate glucocorticoid responsiveness.
Original languageUndefined/Unknown
Pages (from-to)670-686
Number of pages17
JournalNature Reviews Endocrinology
Volume9
Issue number11
DOIs
Publication statusPublished - 2013

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