title: Novel causes of generalized glucocorticoid resistance.
abstract: Glucocorticoid resistance is a rare condition characterized by generalized, partial, target-tissue insensitivity to glucocorticoids. Compensatory elevations in circulating adrenocorticotropic hormone (ACTH) concentrations lead to increased secretion of cortisol and adrenal steroids with mineralocorticoid and/or androgenic activity, but no clinical evidence of hypercortisolism. The clinical spectrum of the condition is broad, ranging from asymptomatic to severe cases of hyperandrogenism, fatigue and/or mineralocorticoid excess. The molecular basis of glucocorticoid resistance has been ascribed to mutations in the human glucocorticoid receptor (hGR) gene, which impair glucocorticoid signal transduction, thereby altering tissue sensitivity to glucocorticoids. The study of functional defects of natural hGR mutants enhances our understanding of the molecular mechanisms of hGR action and highlights the importance of integrated cellular and molecular signaling mechanisms for maintaining homeostasis and preserving normal physiology.
authors.affiliation: Section on Pediatric Endocrinology, Reproductive Biology and Medicine Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA. evangelia.charmandari@googlemail.com
authors.forename: E
authors.initials: E
authors.lastname: Charmandari
authors.forename: T
authors.initials: T
authors.lastname: Kino
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D004351:Drug Resistance; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D009154:Mutation; D011965:Receptors, Glucocorticoid / Q000235:genetics; D015398:Signal Transduction
chemical_list: D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D000324:Adrenocorticotropic Hormone