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Familial/Sporadic Glucocorticoid Resistance: Clinical Phenotype and Molecular Mechanisms
Author(s) -
CHARMANDARI EVANGELIA,
KINO TOMOSHIGE,
CHROUSOS GEORGE P.
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1321.014
Subject(s) - glucocorticoid , glucocorticoid receptor , endocrinology , mineralocorticoid , medicine , mineralocorticoid receptor , phenotype , biology , receptor , signal transduction , adrenocorticotropic hormone , hormone , gene , genetics
A bstract : Glucocorticoids regulate a variety of biologic processes and exert profound influences on many physiologic functions. Their actions are mediated by the glucocorticoid receptor (GR), which belongs to the nuclear receptor family of ligand‐dependent transcription factors. Alterations in tissue sensitivity to glucocorticoids may manifest as states of resistance or hypersensitivity. Glucocorticoid resistance is a rare, familial or sporadic, condition characterized by generalized, partial target‐tissue resistance to glucocorticoids. Compensatory elevations in circulating adrenocorticotropic hormone (ACTH) concentrations lead to increased production of adrenal steroids with mineralocorticoid and/or androgenic activity and their corresponding clinical manifestations, as well as increased urinary free‐cortisol excretion in the absence of symptomatology suggestive of hypercortisolism. The molecular basis of the condition has been ascribed to mutations in the GR gene, which impair normal glucocorticoid signal transduction, altering tissue sensitivity to glucocorticoids. The present review focuses on the mechanisms of GR action and the clinical manifestations and molecular mechanisms of familial/sporadic glucocorticoid resistance.