Familial/sporadic glucocorticoid resistance clinical phenotype and molecular mechanisms

Evangelia Charmandari, Tomoshige Kino, George P. Chrousos

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

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-clependent 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 adrenocorticotropfc 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.

Original languageEnglish
Pages (from-to)168-181
Number of pages14
JournalAnnals of the New York Academy of Sciences
Volume1024
DOIs
Publication statusPublished - 2004
Externally publishedYes

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Glucocorticoids
Glucocorticoid Receptors
Phenotype
Mineralocorticoids
Tissue
Cushing Syndrome
Cytoplasmic and Nuclear Receptors
Nuclear Family
Hydrocortisone
Signal Transduction
Hypersensitivity
Transcription Factors
Steroids
Signal transduction
Hormones
Ligands
Mutation
Glucocorticoid Receptor Deficiency
Familial
Genes

Keywords

  • Glucocorticoid receptor
  • Glucocorticoid resistance
  • Mutations in the GR gene
  • Tissue sensitivity to glucocorticoids

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Familial/sporadic glucocorticoid resistance clinical phenotype and molecular mechanisms. / Charmandari, Evangelia; Kino, Tomoshige; Chrousos, George P.

In: Annals of the New York Academy of Sciences, Vol. 1024, 2004, p. 168-181.

Research output: Contribution to journalArticle

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