GLUCOCORTICOID AND MINERALOCORTICOID RECEPTORS: Biology and Clinical Relevance
Abstract
Mineralocorticoid and glucocorticoid receptors act as homodimers via canonical pentadecamer hormone response elements to regulate transcription. Glucocorticoid, but as yet not mineralocorticoid, receptors have been shown also to modulate AP-1- and NF kappa B-induced transcription by direct protein-protein interactions. The role of 11 beta-hydroxysteroid dehydrogenase in conferring aldosterone specificity on epithelial mineralocorticoid receptors has been proven by the demonstration of sequence mutations in all cases of apparent mineralocorticoid excess examined to date. The autosomal form of aldosterone resistance (pseudohypoaldosteronism) has been shown to reflect loss-of-function mutations in epithelial sodium channel subunit sequence. (Patho)physiological roles for aldosterone and glucocorticoid membrane receptors, and for the recently described nuclear receptors for 11-ketosteroids in 11 beta-hydroxysteroid dehydro-genase-protected epithelia, remain to be established.
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Once bound to their hormone ligand, mineralocorticoid receptors and glucocorticoid receptors act as transcription factors by migrating to the nucleus and binding to hormone response elements often found in gene promoters.
“Once bound to their hormone ligand, MRs and GRs act as transcription factors by migrating to the nucleus and binding to hormone response elements often found in gene promoters (Funder, 1997).”
From The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review (2023) · cites this paper as Funder, 1997
Corticosteroids are capable of binding to two intracellular receptors: mineralocorticoid receptors and glucocorticoid receptors.
“These corticosteroids are commonly known as “stress hormones,” and are capable of binding to two intracellular receptors: mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs).”
From The Epigenetics of Anxiety Pathophysiology: A DNA Methylation and Histone Modification Focused Review (2023) · cites this paper as Funder, 1997
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“Glucocorticoids (cortisol in humans and corticosterone in rodents) act through two types of nuclear receptors: the mineralocorticoid receptor (MR), a high-affinity receptor that is activated by basal concentrations of these hormones, and the glucocorticoid receptor (GR), a low-affinity receptor that is activated in th…”
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What pharmacologists can learn from recent advances in estrogen signalling.
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“The effects of corticosteroids are determined through asymmetric distribution of the mineralocorticoid and glucocorticoid nuclear hormone receptors (MR and GR) and the protective effects of 11b-hydroxysteroid dehydrogenase, which selectively metabolizes glucocorticoids (2, 20, 31).”
Background50th Anniversary of Aldosterone
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“We therefore compared the effect of corticosterone with that of dexamethasone, which poorly activates MR.(16) Dexamethasone induced all four mRNAs in a dose-dependent manner over 24 h (Figures 3a–d).”
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“Hormone-bound receptor then trafficks into the nucleus where it seeks out, and interacts with, specific regions of the DNA to control the rate at which target genes are ‘switched on’ (activation) or ‘switched off ’ (repression) (figure 1) (Tsai & O’Malley 1994; Funder 1997).”
Glucocorticoid and mineralocorticoid resistance/hypersensitivity syndromes
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“The MR of the distal convoluted tubule and possibly other mineralocorticoid target tissues are protected from the actions of cortisol by expression of 11 -hydroxysteroid dehydrogenase type 2, which converts cortisol into the inactive cortisone (Funder 1997).”
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Stress and tinnitus—from bedside to bench and back
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“The genomic reactions occur due to the fact that both GRs and mineralcorticoid receptors are cytoplasmic, ligand-activated transcription factors (Funder, 1997).”
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“Glucocorticoid actions are mediated by two receptor types: type 1, or mineralocorticoid receptor (MR), and type 2, or glucocorticoid receptor (GR), both of which have been cloned in humans[3,4,28].”
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“GRs are distributed throughout the brain, but mostly in hypothalamic neurons and corticotrophs (Jacobson and Sapolsky, 1991; Funder, 1997), whereas MRs are present in the hypothalamus and in the greatest numbers in the hippocampus (Ratka et al.”
BackgroundAldosterone-induced organ damage: plasma aldosterone level and inappropriate salt status.
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“Two types of intracellular GC receptors are expressed in the brain: the high aYnity type I receptor (also called the mineralocorticoid receptor; MR), and the lower aYnity type II receptor (also called the glucocorticoid receptor; GR) (see Funder, 1997, for review).”
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“After GR binding, these activated receptors are translocated to the nucleus where they bind to the glucocorticoid responsive elements (GRE) and affect the transcriptional activity of target genes (Funder, 1997).”
BackgroundWork-related stress in an emergency medical dispatch center.
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“Both exert effects predominantly through binding to DNA, though rapid non-genomic signalling has also been reported for both (reviewed Funder (1997), Buckingham (2006), Dooley et al. (2012) and from Bioscientifica.com at 11/14/2019 09:30:57PM via free access Jo u rn a l o f M o le cu la r E n d o…”
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“Together with GR, MR is found in heart tissue [32–34].”
Haque, M., Kaminsky, L., Abdulqadir, R. F., Engers, J., Kovtunov, E., Rawat, M., Al-Sadi, R., & Ma, T. Y. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1348010 · Cited by 71 · see citing works
“The IKK catalytic subunits enzymatically catalyze the phosphorylation, ubiquitination, and degradation of I k B-a protein and the concomitant NF-k B p50/ p65 activation (124, 125).”
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“They exert their function in different target tissues by binding two intracellular receptors: the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) [2], and are able to regulate multiple metabolic pathways, including glycolysis/gluconeogenesis, fatty acids and cholesterol metabolism [3].”
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“Given MR’s importance in regulating sodium balance (via ALDO binding) in mammals [22], we expected to see greater MR capacity than GR capacity in house sparrow.”
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Regulation of S100A8 by Glucocorticoids1
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“2A) called the glucocorticoid response element (GRE) found in the promoter region of target genes, resulting in either transcriptional activation or repression (reviewed in Funder [94]).”
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The Bacterial and Viral Agents of BRDC: Immune Evasion and Vaccine Developments
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- Authors
- Funder, M.
- Affiliations
- Baker Medical Research Institute, Prahran, 3181 Australia
- Venue
- Annual Review of Medicine
- Publisher
- Annual Reviews
- Published
- 1997-02
- Volume
- 48
- Issue
- 1
- Pages
- 231-240
- ISSN
- 0066-4219 (ISSN-L)
- 1545-326X
- OpenAlex
- W2128569914
- Cited by
- 320
- References
- 0
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 10 · 2023: 3 · 2022: 2 · 2021: 13 · 2020: 6 · 2019: 10 · 2018: 8 · 2017: 13 · 2016: 17 · 2015: 13 · 2014: 21 · 2013: 16 · 2012: 18
- FWCI
- 2.68
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- glucocorticoid receptor, mineralocorticoid receptor, nuclear receptors, hormone response elements, transcriptional regulation, AP-1, NF-κB, protein-protein interaction, 11β-hydroxysteroid dehydrogenase, aldosterone, apparent mineralocorticoid excess, pseudohypoaldosteronism, epithelial sodium channel, cell surface receptors
- MeSH terms
- Aldosterone, Animals, DNA Mutational Analysis, Humans, Receptors, Glucocorticoid, Gene Expression, NF-kappa B, Receptors, Mineralocorticoid, Transcription Factor AP-1, Mice
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