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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Dynamic Regulation of AMPAR Phosphorylation In Vivo Following Acute Behavioral Stress
Caudal, D., Rame, M., Jay, T. M., & Godsil, B. P. (2016) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-016-0332-9 · Cited by 19
“Classically, these receptors are known to mediate stress effects by affecting gene expression (Reul and de Kloet 1985; Funder 1997; Herman et al. 2003), yet there is also evidence for a population of membrane-localized MRs and GRs involved”
Background
Psychological Stress as a Modulator of Functional Recovery Following Spinal Cord Injury
Bouchard, S. M., & Hook, M. A. (2014) · Frontiers in Neurology · doi:10.3389/fneur.2014.00044 · Cited by 26
There is no correlation between glucocorticoid receptor mRNA expression and protein binding in the brains of house sparrows (Passer domesticus)
Medina, C. O., Lattin, C. R., McVey, M., & Romero, L. M. (2013) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2013.07.008 · Cited by 21
“In birds and mammals, there are two intracellular corticosteroid receptors that bind to CORT, as well as a possible membrane-bound receptor that is not the focus of this study (Breuner and Orchinik, 2009; Breuner et al., 2003; Funder, 1997; Orchinik et al., 1991; Schmidt et al., 2010).”
Background
Generalized and tissue specific glucocorticoid resistance
Martins, C. S., & de Castro, M. (2021) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2021.111277 · Cited by 30
The serum and glucocorticoid-regulated protein kinases (SGK) stimulate bovine herpesvirus 1 and herpes simplex virus 1 productive infection
Kook, I., & Jones, C. (2016) · Virus Research · doi:10.1016/j.virusres.2016.06.007 · Cited by 21
Disorders of mineralocorticoid synthesis
Connell, J., Fraser, R., & Davies, E. (2001) · Best Practice & Research Clinical Endocrinology & Metabolism · doi:10.1053/beem.2000.0118 · Cited by 20
In vivo tissue specific modulation of rat insulin receptor gene expression in an experimental model of mineralocorticoid excess
Campión, J., Lahera, V., Cachofeiro, V., Maestro, B., Dávila, N., Carranza, M. C., & Calle, C. (1998) · Molecular and Cellular Biochemistry · doi:10.1023/a:1006871309864 · Cited by 18
“The possible mediation of a mechanism of MR/GR interaction [9, 37, 38] in the DOCA-induced increase in hepatic IR mRNA levels, requires further investigation.”
Background
Effects of aldosterone on Cx43 gap junction expression in neonatal rat cultured cardiomyocytes.
Suzuki, S., Ohkusa, T., Sato, T., Yoshida, M.-A., Yasui, K., Miwa, K., Lee, J.-K., Yano, M., Kodama, I., & Matsuzaki, M. (2009) · Circulation Journal · doi:10.1253/circj.cj-08-1065 · Cited by 19
Different regulation of cardiac and renal corticosteroid receptors in aldosterone-salt treated rats: effect of hypertension and glucocorticoids.
Silvestre, J., Robert, V., Escoubet, B., Heymes, C., Oubenaissa, A., Desopper, C., Swynghedauw, B., & Delcayre, C. (2000) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.2000.1159 · Cited by 19
Regulation of nitric oxide and prostaglandin E2 production by CSAIDSTM (SB203580) in murine macrophages and bovine chondrocytes stimulated with LPS
Patel, R., Attur, M., Dave, M., Kumar, S., Lee, J. C., Abramson, S. B., & Amin, A. R. (1999) · Inflammation Research · doi:10.1007/s000110050469 · Cited by 19
Changes in processes downstream of the hypothalamus are associated with seasonal follicle development in a songbird, the dark-eyed junco (Junco hyemalis).
Needham, K. B., Burns, C. B., Graham, J. L., Bauer, C. M., Kittilson, J., Ketterson, E., Hahn, T., & Greives, T. (2019) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2018.10.012 · Cited by 18
Low dose combination steroids control autoimmune mouse hearing loss
Trune, D. R., & Kempton, J. B. (2010) · Journal of Neuroimmunology · doi:10.1016/j.jneuroim.2010.07.026 · Cited by 17
“Glucocorticoids, in addition to their role in immune suppression, have a significant mineralocorticoid receptormediated function that includes Na+ and K+ transport (Rupprecht et al., 1993; Funder, 1997).”
Cytosolic glucocorticoid receptor in the testis of Bufo arenarum: Seasonal changes in its binding parameters
Denari, D., & Ceballos, N. R. (2006) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2006.01.006 · Cited by 20
Regulation of neurotropic herpesvirus productive infection and latency-reactivation cycle by glucocorticoid receptor and stress-induced transcription factors
Ostler, J. B., Sawant, L., Harrison, K. S., & Jones, C. (2021) · Vitamins and hormones · doi:10.1016/bs.vh.2021.06.005 · Cited by 17
Glucocorticoid and mineralocorticoid receptor expression in critical illness: A narrative review
Vassiliou, A. G., Athanasiou, N., Vassiliadi, D. A., Jahaj, E., Keskinidou, C., Kotanidou, Α., & Dimopoulou, I. (2021) · World Journal of Critical Care Medicine · doi:10.5492/wjccm.v10.i4.102 · Cited by 19
Discovery of novel oxazolidinedione derivatives as potent and selective mineralocorticoid receptor antagonists.
Yang, C., Shen, H. C., Wu, Z.-C., Chu, H. D., Cox, J. M., Balsells, J., Crespo, A., Brown, P., Zamlynny, B., Wiltsie, J., et al. (2013) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2013.05.077 · Cited by 16
In-vivo regulation of Krüppel-like factor 9 by corticosteroids and their receptors across tissues in tadpoles of Xenopus tropicalis.
Shewade, L. H., Schneider, K. A., Brown, A. C., & Buchholz, D. (2017) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2017.02.007 · Cited by 15
Evaluation of Glucocorticoid Sensitivity and Its Potential Clinical Applicability
Longui, C. A., & Faria, C. D. C. (2009) · Hormone Research in Paediatrics · doi:10.1159/000223413 · Cited by 18
Blocking the Glucocorticoid Receptor with RU-486 Does Not Prevent Glucocorticoid Control of Autoimmune Mouse Hearing Loss
Trune, D., & Kempton, J. (2009) · Audiology and Neurotology · doi:10.1159/000241899 · Cited by 14
The Acute Anticonvulsant Effects of Deoxycorticosterone in Developing Rats: Role of Metabolites and Mineralocorticoid‐receptor Responses
Edwards, H. E., Vimal, S., & Burnham, W. (2005) · Epilepsia · doi:10.1111/j.1528-1167.2005.00295.x · Cited by 14
Aldosterone and anti-aldosterone effects in cardiovascular diseases and diabetic nephropathy.
Ambroisine, M., Milliez, P., Nehmé, J., Pasquier, A., de Angelis, N., Mansier, P., Swynghedauw, B., & Delcayre, C. (2004) · Diabetes & Metabolism · doi:10.1016/s1262-3636(07)70122-2 · Cited by 14
“Thus, other mechanisms are required to explain the aldosterone specific binding [2], or one must admit that the cardiac MR is predominantly occupied by glucocorticoids [51].”
Background
How Useful Is Corticosteroid Treatment in Cochlear Disorders?
Lamm, K., & Arnold, W. J. (1999) · Oto-Rhino-Laryngologia Nova · doi:10.1159/000027909 · Cited by 16
Stress Can Induce Bovine Alpha-Herpesvirus 1 (BoHV-1) Reactivation from Latency
El-mayet, F. S., & Jones, C. (2024) · Viruses · doi:10.3390/v16111675 · Cited by 14
SUMO E3 ligase PIAS1 is a potential biomarker indicating stress susceptibility
Lin, H., Liu, Y.-S., Huang, C., Cathomas, F., Liu, K., Wang, J., Cheng, H., Lai, S., Liu, Y., Chen, C., et al. (2020) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2020.104800 · Cited by 14
Biotransformation of the mineralocorticoid receptor antagonists spironolactone and canrenone by human CYP11B1 and CYP11B2: Characterization of the products and their influence on mineralocorticoid receptor transactivation
Schiffer, L., Müller, A.-R., Hobler, A., Brixius‐Anderko, S., Zapp, J., Hannemann, F., & Bernhardt, R. (2016) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2016.04.004 · Cited by 14
Corticosterone regulates fear memory via Rac1 activity in the hippocampus
Gan, P., Ding, Z.-Y., Gan, C., Mao, R., Zhou, H., Xu, L., & Zhou, Q. (2016) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2016.05.011 · Cited by 14
“GRs translocate to the nucleus after binding to CORT, where they operate as transcriptional regulators of gene expression (Herman et al., 2003; Funder, 1997; Reul and de Kloet, 1985).”
Background
Discovery of Benzimidazole Oxazolidinediones as Novel and Selective Nonsteroidal Mineralocorticoid Receptor Antagonists
Yang, C., Balsells, J., Chu, H. D., Cox, J. M., Crespo, A., Ma, X., Contino, L. C., Brown, P. N., Gao, S., Zamlynny, B., et al. (2015) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.5b00010 · Cited by 13
The acute effect of fludrocortisone on basal and hCRH-stimulated hypothalamic–pituitary–adrenal (HPA) axis in humans
Karamouzis, I., Berardelli, R., Marinazzo, E., D’Angelo, V., Zinnà, D., Minetto, M. A., Zichi, C., Fussotto, B., Giordano, R., Ghigo, E., et al. (2012) · Pituitary · doi:10.1007/s11102-012-0435-3 · Cited by 13
“Animal studies demonstrated that GRs have a widespread distribution in the central nervous system, but are more abundant in hypothalamic neurons and corticotroph cells in the pituitary gland [3, 4, 7].”
BackgroundInfluential
Hypophyseal corticosteroids stimulate somatotrope differentiation in the embryonic chicken pituitary gland
Zheng, J., Takagi, H., Tsutsui, C., Adachi, A., & Sakai, T. (2008) · Histochemistry and Cell Biology · doi:10.1007/s00418-007-0364-9 · Cited by 13
“Although it has been reported that mineralocorticoids also bind to both GR and MR (Funder 1997; Savory et al. 2001), the eVect of mineralocorticoids on GH mRNA expression and the roles of their receptors in somatotrope diVerentiation have not been elucidated.”
Background
Leukemia inhibitory factor regulates glucocorticoid receptor expression in the hypothalamic-pituitary-adrenal axis
Kariagina, A., Zonis, S., Afkhami, M., Romanenko, D., & Chesnokova, V. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00577.2004 · Cited by 13
Glucococorticoid receptor activation exacerbates aminoglycoside-induced damage to the zebrafish lateral line
Hayward, T., Young, A. P., Jiang, A., Crespi, E. J., & Coffin, A. B. (2019) · Hearing Research · doi:10.1016/j.heares.2019.03.002 · Cited by 10
Cardiomyocyte mineralocorticoid receptor function post myocardial infarction.
Fraccarollo, D., & Bauersachs, J. (2011) · Trends in cardiovascular medicine · doi:10.1016/j.tcm.2012.02.003 · Cited by 12
Stress and long-term synaptic depression
Rowan, M. J., Anwyl, R., & Xu, L. (1998) · Molecular Psychiatry · doi:10.1038/sj.mp.4000429 · Cited by 12
Interleukin 2 up-regulates glucocorticoid receptor number in human peripheral blood mononuclear cells and the osteosarcoma cell line Saos-2 in vitro.
Sartori, M., Masera, R., Staurenghi, A., Racca, S., & Angeli, A. (1998) · Steroids · doi:10.1016/s0039-128x(98)00023-3 · Cited by 12
Nebennierenrinde und Steroide
Milde, A. S., Böttiger, B. W., & Morcos, M. (2005) · Der Anaesthesist · doi:10.1007/s00101-005-0867-5 · Cited by 14
Salt Appetite and its Effects on Cardiovascular Risk in Primary Aldosteronism
Adolf, C., Schneider, H., Heinrich, D. A., Handgriff, L., & Reincke, M. (2020) · Hormone and Metabolic Research · doi:10.1055/a-1116-2407 · Cited by 11
“, kidney, colon, sweat and salivary gland) it is the enzyme 11β-HSD2, which converts cortisol into its inactive metabolite cortisone, with parallel conversion of the cofactor NAD + to NADH, thereby rendering aldosterone to the main activator of epithelial MR [44, 94, 95].”
Background
Glucocorticoid Receptor Binding Inhibits an Intronic IL33 Enhancer and is Disrupted by rs4742170 (T) Allele Associated with Specific Wheezing Phenotype in Early Childhood
Gorbacheva, A. M., Kuprash, D. V., & Mitkin, N. A. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19123956 · Cited by 11
“High levels of cytosolic GR are constitutively expressed by lung epithelium [38], GR activity, and nuclear translocation is triggered by binding to cortisol [39].”
Background
Cardiac phenylethanolamine N-methyltransferase: localization and regulation of gene expression in the spontaneously hypertensive rat
Peltsch, H., Khurana, S., Byrne, C. J., Nguyen, P., Khaper, N., Kumar, A., & Tai, T. C. (2015) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/cjpp-2015-0303 · Cited by 10
“The GR, an intracellular receptor, must be activated by GC binding, which results in the translocation of activated GR to the nucleus, whereby it can regulate the transcription of many genes (Yamamoto 1985; Funder 1997), including PNMT (Tai et al.”
Background
Somatotropin response in vitro to corticosterone and triiodothyronine during chick embryonic development: Involvement of type I and type II glucocorticoid receptors.
Heuck, K., Ellestad, L., Proudman, J., & Porter, T. E. (2009) · Domestic Animal Endocrinology · doi:10.1016/j.domaniend.2008.11.005 · Cited by 10
Persistent NF-κB activation in renal epithelial cells in a mouse model of HIV-associated nephropathy
Martinka, S., & Bruggeman, L. (2006) · doi:10.1152/ajprenal.00208.2005 · Cited by 10
“An important part of the anti-inflammatory action of corticosteroids is through the suppression of NF-κB (14).”

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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