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The Multifaceted Mineralocorticoid Receptor
Abstract
The primary adrenal cortical steroid hormones, aldosterone, and the glucocorticoids cortisol and corticosterone, act through the structurally similar mineralocorticoid (MR) and glucocorticoid receptors (GRs). Aldosterone is crucial for fluid, electrolyte, and hemodynamic homeostasis and tissue repair; the significantly more abundant glucocorticoids are indispensable for energy homeostasis, appropriate responses to stress, and limiting inflammation. Steroid receptors initiate gene transcription for proteins that effect their actions as well as rapid non‐genomic effects through classical cell signaling pathways. GR and MR are expressed in many tissues types, often in the same cells, where they interact at molecular and functional levels, at times in synergy, others in opposition. Thus the appropriate balance of MR and GR activation is crucial for homeostasis. MR has the same binding affinity for aldosterone, cortisol, and corticosterone. Glucocorticoids activate MR in most tissues at basal levels and GR at stress levels. Inactivation of cortisol and corticosterone by 11β‐HSD2 allows aldosterone to activate MR within aldosterone target cells and limits activation of the GR. Under most conditions, 11β‐HSD1 acts as a reductase and activates cortisol/corticosterone, amplifying circulating levels. 11β‐HSD1 and MR antagonists mitigate inappropriate activation of MR under conditions of oxidative stress that contributes to the pathophysiology of the cardiometabolic syndrome; however, MR antagonists decrease normal MR/GR functional interactions, a particular concern for neurons mediating cognition, memory, and affect. © 2014 American Physiological Society. Compr Physiol 4:965‐994, 2014.
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“Corticosterone can be converted to 11-dehydrocorticosterone by the action of HSD11B2 in the kidney, which prevents the activation of the mineralocorticoid receptor (MR) by corticosterone”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [219]
In the citing paper
“though corticosterone’s MR-activating potency is considerably lower than that of aldosterone [219].”
From Human steroid biosynthesis, metabolism and excretion are differentially reflected by serum and urine steroid metabolomes: a comprehensive review (2019) · cites this paper as [219]
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Steroidal and non-steroidal mineralocorticoid receptor antagonists in cardiorenal medicine
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Schiffer, L., Barnard, L., Baranowski, E. S., Gilligan, L. C., Taylor, A. E., Arlt, W., Shackleton, C. H. L., & Storbeck, K.-H. (2019) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2019.105439 · Cited by 450
“Corticosterone can be converted to 11-dehydrocorticosterone by the action of HSD11B2 in the kidney, which prevents the activation of the mineralocorticoid receptor (MR) by corticosterone though corticosterone’s MR-activating potency is considerably lower than that of aldosterone [219].”
Stress and Obesity: Are There More Susceptible Individuals?
van der Valk, E. S., Savas, M., & van Rossum, E. F. C. (2018) · Current Obesity Reports · doi:10.1007/s13679-018-0306-y · Cited by 402
Glucocorticoids and bone: consequences of endogenous and exogenous excess and replacement therapy
Hardy, R. S., Zhou, H., Seibel, M. J., & Cooper, M. S. (2018) · Endocrine Reviews · doi:10.1210/er.2018-00097 · Cited by 258
The regulation of adipose tissue health by estrogens
Steiner, B. M., & Berry, D. C. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.889923 · Cited by 171
Metadata
- Authors
- Gomez‐Sanchez, E., & Gomez‐Sanchez, C. E.
- Affiliations
- G.V.(Sonny) Montgomery V.A. Medical Center and Department of Medicine University of Mississippi Medical Center Jackson Mississippi
- Venue
- Comprehensive Physiology
- Publisher
- Wiley
- Published
- 2014-07
- Volume
- 4
- Issue
- 3
- Pages
- 965-994
- ISSN
- 2040-4603 (ISSN-L)
- OpenAlex
- W4409120372
- Semantic Scholar
- 7a31ae1a885a350aaecee2d5692c77add13a0b62
- Cited by
- 55
- References
- 505
- Citations by year
- 2026: 25 · 2025: 8 · 2024: 6 · 2023: 3 · 2022: 2 · 2020: 2 · 2019: 1 · 2018: 3 · 2017: 3 · 2016: 1 · 2015: 1
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Comprehensive physiology (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
- mineralocorticoid receptor, glucocorticoid receptor, aldosterone, cortisol, corticosterone, 11β-hydroxysteroid dehydrogenase type 2, 11β-hydroxysteroid dehydrogenase type 1, non-genomic steroid action, receptor interaction, oxidative stress, cardiometabolic syndrome, mineralocorticoid receptor antagonists, glucocorticoid receptor antagonist, stress response, inflammation, fluid and electrolyte balance
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