Glucocorticoid and mineralocorticoid receptors and associated diseases

Tomoshige Kino, George P. Chrousos

Research output: Contribution to journalReview article

52 Citations (Scopus)

Abstract

Adrenal corticosteroids, ie. glucocorticoids and mineralocorticoids, play important physiological roles in humans. Their actions are mediated by intracellular receptor molecules, the glucocorticoid receptor (GR) and mineralocorticoid receptor (MR), which function as hormone-dependent transcription factors. Ligand-activated receptors modulate the transcription rates of responsive genes by interacting with responsive elements in the promoters of these genes or by influencing the activities of other transcription factors, via protein-protein interactions. Natural inactivating mutations of the GR or MR genes have been reported in humans with significant clinical phenotypes. The former causes sporadic or familial glucocorticoid resistance characterized by generalized partial insensitivity of tissues to glucocorticoids and subsequent activation of the hypothalamic/pituitary/adrenal axis with resultant hyperandrogenism in children and women and/or mineralocorticoid excess symptoms in both sexes. The latter develop pseudohypoaldosteronism type 1, i.e. hypotension and hyperkalaemic acidosis, as a result of reduced aldosterone actions in the kidney. An activating mutation in the MR gene causing early-onset, periodic hypertension was reported recently. The biological relevance of the GR and MR receptors was also addressed in mice whose GR or MR genes were inactivated or modified by gene targeting. The results were generally confirmatory of the concepts obtained by the human studies. Similarly, natural, compensated glucocorticoid and/or mineralocorticoid 'resistance' were described in several mammalian species, including non-human primates and rodents. Here we discuss the actions of GR and MR and the molecular defects of naturally occuring mutations in these receptors with associated pathophysiological changes.

Original languageEnglish
Pages (from-to)137-155
Number of pages19
JournalEssays in Biochemistry
Volume40
Publication statusPublished - 2004
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry

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