Cited by 320Hormonal Regulation and HypertensionEstrogen and related hormone effectsAdrenal Hormones and Disorders

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GLUCOCORTICOID AND MINERALOCORTICOID RECEPTORS: Biology and Clinical Relevance

Funder, MD, John W.·1997·Annual Review of Medicine

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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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Rog‐Zielinska, E. A., Richardson, R. V., Denvir, M. A., & Chapman, K. E. (2013) · Journal of Molecular Endocrinology · doi:10.1530/jme-13-0204 · Cited by 84
“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…”
Background
Pharmacological characterization of intracellular, membrane, and plasma binding sites for corticosterone in house sparrows
Breuner, C. W., & Orchinik, M. (2009) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2009.01.027 · Cited by 70
The Stress Hormone Corticosterone Increases Synaptic α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors via Serum- and Glucocorticoid-inducible Kinase (SGK) Regulation of the GDI-Rab4 Complex
Liu, W., Yuen, E. Y., & Yan, Z. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.050229 · Cited by 78
Contribution of glucocorticoid–mineralocorticoid receptor pathway on the obesity-related adipocyte dysfunction
Hirata, A., Maeda, N., Nakatsuji, H., Hiuge-Shimizu, A., Okada, T., Funahashi, T., & Shimomura, I. (2012) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2012.01.139 · Cited by 88
Selective Binding of Steroid Hormone Receptors to Octamer Transcription Factors Determines Transcriptional Synergism at the Mouse Mammary Tumor Virus Promoter
Préfontaine, G. G., Walther, R. F., Giffin, W., Lemieux, M. E., Pope, L., & Haché, R. J. G. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.38.26713 · Cited by 80
Non-genomic effect of glucocorticoids on cardiovascular system
Lee, S. R., Kim, H. K., Youm, J. B., Dizon, L. A., Song, I. S., Jeong, S. H., Seo, D. Y., Ko, K. S., Rhee, B. D., Kim, N., et al. (2012) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-012-1155-2 · Cited by 78
“Together with GR, MR is found in heart tissue [32–34].”
Lactobacillus acidophilus inhibits the TNF-α-induced increase in intestinal epithelial tight junction permeability via a TLR-2 and PI3K-dependent inhibition of NF-κB activation
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
“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).”
Background
Sex and stress steroids in adolescence: Gonadal regulation of the hypothalamic–pituitary–adrenal axis in the rat
Green, M. R., & McCormick, C. M. (2016) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2016.02.004 · Cited by 84
Mineralocorticoid receptor in adipocytes and macrophages: A promising target to fight metabolic syndrome
Marzolla, V., Armani, A., Feraco, A., Martino, M. U. D., Fabbri, A., Rosano, G. M. C., & Caprio, M. (2014) · Steroids · doi:10.1016/j.steroids.2014.05.001 · Cited by 75
“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].”
Background
Pharmacological characterization of intracellular glucocorticoid receptors in nine tissues from house sparrow (Passer domesticus).
Lattin, C., Waldron-Francis, K., Richardson, J. W., de Bruijn, R., Bauer, C. M., Breuner, C., & Romero, L. M. (2012) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2012.08.007 · Cited by 69
“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.”
Background
Mineralocorticoid selectivity: Molecular and cellular aspects
Farman, N., & Bocchi, B. (2000) · Kidney International · doi:10.1046/j.1523-1755.2000.00976.x · Cited by 63
Glucocorticoids Stimulate Inflammatory 5‐Lipoxygenase Gene Expression and Protein Translocation in the Brain
Uz, T., Dwivedi, Y., Savani, P. D., Impagnatiello, F., Pandey, G. N., & Manev, H. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0730693.x · Cited by 61
Mineralocorticoids in the Heart and Vasculature: New Insights for Old Hormones
Lother, A., Moser, M., Bode, C., Feldman, R. D., & Hein, L. (2014) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010814-124302 · Cited by 65
Hypothalamus-Pituitary-Adrenal Hyperactivity in Human Aging Is Partially Refractory to Stimulation by Mineralocorticoid Receptor Blockade
Giordano, R., Bo, M., Pellegrino, M., Vezzari, M., Baldi, M., Picu, A., Balbo, M. L., Bonelli, L., Migliaretti, G., Ghigo, E., et al. (2005) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2005-0105 · Cited by 61
Regulation of S100A8 by Glucocorticoids1
Hsu, K. J., Passey, R., Endoh, Y., Rahimi, F., Youssef, P., Yen, T., & Geczy, C. (2005) · Journal of Immunology · doi:10.4049/jimmunol.174.4.2318 · Cited by 65
Role of mineralocorticoid receptors on the hypothalamus–pituitary–adrenal axis in humans
Berardelli, R., Karamouzis, I., D’Angelo, V., Zichi, C., Fussotto, B., Giordano, R., Ghigo, E., & Arvat, E. (2012) · Endocrine · doi:10.1007/s12020-012-9750-8 · Cited by 62
Aldosterone promotes fibronectin production through a Smad2-dependent TGF-beta1 pathway in mesangial cells.
Lai, L., Chen, J., Hao, C.-M., Lin, S.-T., & Gu, Y. (2006) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1016/j.bbrc.2006.07.057 · Cited by 64
Glucose metabolism in patients with subclinical Cushing’s syndrome
Giordano, R., Guaraldi, F., Berardelli, R., Karamouzis, I., D’Angelo, V., Marinazzo, E., Picu, A., Ghigo, E., & Arvat, E. (2012) · Endocrine · doi:10.1007/s12020-012-9628-9 · Cited by 64
Induction of 11β-HSD 1 and Activation of Distinct Mineralocorticoid Receptor- and Glucocorticoid Receptor-Dependent Gene Networks in Decidualizing Human Endometrial Stromal Cells
Kuroda, K., Venkatakrishnan, R., Salker, M. S., Lucas, E. S., Shaheen, F., Kuroda, M., Blanks, A., Christian, M., Quenby, S., & Brosens, J. J. (2013) · Molecular Endocrinology · doi:10.1210/me.2012-1247 · Cited by 63
Modulation of synaptic plasticity by exercise
Bettio, L. E. B., Thacker, J. S., Hutton, C. P., & Christie, B. R. (2019) · International review of neurobiology · doi:10.1016/bs.irn.2019.07.002 · Cited by 87
Nuclear Receptors in Leydig Cell Gene Expression and Function1
Martin, L. J., & Tremblay, J. J. (2010) · Biology of Reproduction · doi:10.1095/biolreprod.110.083824 · Cited by 62
“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]).”
Background
Aldosterone and the heart: towards a physiological function?
Delcayre, C., & Silvestre, J. (1999) · Cardiovascular Research · doi:10.1016/s0008-6363(99)00088-7 · Cited by 62
The Bacterial and Viral Agents of BRDC: Immune Evasion and Vaccine Developments
Bell, R. L., Turkington, H. L., & Cosby, S. L. (2021) · Vaccines · doi:10.3390/vaccines9040337 · Cited by 67
It takes two to tango: Dimerisation of glucocorticoid receptor and its anti-inflammatory functions
Nixon, M., Andrew, R., & Chapman, K. E. (2012) · Steroids · doi:10.1016/j.steroids.2012.09.013 · Cited by 62
Expression and roles of steroidogenic acute regulatory (StAR) protein in 'non-classical', extra-adrenal and extra-gonadal cells and tissues
Anuka, E., Gal, M., Stocco, D. M., & Orly, J. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.02.003 · Cited by 60
Aldosterone rapidly represses protein kinase C activity in neonatal rat cardiomyocytes in vitro.
Sato, A., Liu, J.-P., & Funder, J. W. (1997) · Endocrinology · doi:10.1210/endo.138.8.5352 · Cited by 60
“Finally, in epithelial MR corticosterone and cortisol mimic the action of aldosterone, whereas in nonepithelial MR the physiologic glucocorticoids act, like spironolactone, as aldosterone antagonists (34); again, the basis for this difference is unclear.”
Adrenal and sex steroid receptor evolution: environmental implications.
Baker, M. (2001) · Journal of Molecular Endocrinology · doi:10.1677/jme.0.0260119 · Cited by 58
“By inactivating cortisol in the kidney, 11 -HSD-type 2 prevents unwanted occupancy of the MR by cortisol, which allows aldosterone to regulate mineralocorticoid responsive genes (Monder 1991, Edwards et al. 1996, Funder 1997).”
BackgroundMethodInfluential
Nongenomic steroid actions: fact or fantasy?
Christ, M., Haseroth, K., Falkenstein, E., & Wehling, M. (1999) · Vitamins and hormones · doi:10.1016/s0083-6729(08)60647-0 · Cited by 57
Lithium's role in neural plasticity and its implications for mood disorders
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“eralocorticoid receptors (MRs) on neurons and glia to effect transcriptional regulation (11, 12).”
Background
Aldosterone and mineralocorticoid receptors in regulation of the cardiovascular system and pathological remodelling of the heart and arteries.
Sztechman, D., Czarzasta, K., Cudnoch-Jędrzejewska, A., Szczepańska-Sadowska, E., & Żera, T. (2018) · Journal of Physiology and Pharmacology · doi:10.26402/jpp.2018.6.01 · Cited by 55
Zebrafish 20β-Hydroxysteroid Dehydrogenase Type 2 Is Important for Glucocorticoid Catabolism in Stress Response
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“Additionally, in humans the affinity of cortisol for the mineralocorticoid receptor (MR) is comparable to that of aldosterone, the native MR ligand [24].”
Spironolactone Modulates Expressions of Cardiac Mineralocorticoid Receptor and 11.BETA.-Hydroxysteroid Dehydrogenase 2 and Prevents Ventricular Remodeling in Post-Infarct Rat Hearts
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Mineralocorticoid receptor blockade by canrenoate increases both spontaneous and stimulated adrenal function in humans.
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Cooperativity and complementarity: Synergies in non-classical and classical glucocorticoid signaling
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Combinatorial Effects of the Glucocorticoid Receptor and Krüppel-Like Transcription Factor 15 on Bovine Herpesvirus 1 Transcription and Productive Infection
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Dexamethasone Induces Transcriptional Activation of Bcl-xL Gene and Inhibits Cardiac Injury by Myocardial Ischemia
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“The receptor has α (94 kD) and β (90 kD) isoforms (Bamberger et al., 1996; Funder, 1997; Yudt and Cidlowski, 2002).”
Background
Diagram of the pathways of human steroidogenesis
Häggström, M., & Richfield, D. (2014) · doi:10.15347/wjm/2014.005 · Cited by 51
Transcriptional regulation of matrix metalloprotease gene expression in health and disease
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“Glucocorticoids bind to their hormone-inducible nuclear receptors (GRs) and interact with or transactivate glucocorticoid response elements (GRE) present in the promoters of many genes (62).”
Background
Behavioral stress induces regionally-distinct shifts of brain mineralocorticoid and glucocorticoid receptor levels
Caudal, D., Jay, T., & Godsil, B. (2014) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2014.00019 · Cited by 50
Rapid actions of aldosterone: lymphocytes, vascular smooth muscle and endothelial cells
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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
DOI: 10.1146/annurev.med.48.1.231
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 › Endocrinology › 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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GLUCOCORTICOID AND MINERALOCORTICOID RECEPTORS: Biology and Clinical Relevance

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