Cited by 55Hormonal Regulation and HypertensionEstrogen and related hormone effectsAdrenal Hormones and Disorders

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The Multifaceted Mineralocorticoid Receptor

Gomez‐Sanchez, Elise, Gomez‐Sanchez, Celso E.·2014·Comprehensive Physiology

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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Crossref · 10.1002/j.2040-4603.2014.tb00569.x

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Research works printed but not linked: 13

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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
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
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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