The coming out of the brain mineralocorticoid receptor
Abstract
Corticosteroids - secreted after stress - have profound effects on brain and behavior. These effects are mediated by mineralocorticoid and glucocorticoid receptors, which are abundantly expressed in limbic neurons. The role of mineralocorticoid receptors in higher brain functions has never been well understood. Here we argue that the recently discovered low-affinity membrane version of the mineralocorticoid receptor contributes to the initial phase of the stress reaction; this is complemented by the glucocorticoid receptor which terminates the stress response. This concept may explain why human carriers of a mineralocorticoid receptor gene variant display enhanced neuroendocrine and autonomic responsiveness to a psychological stressor.
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Glucocorticoid receptors are ubiquitously expressed in the brain but most abundant in the PVN and hippocampus; mineralocorticoid receptor expression is mostly confined to limbic sites regulating salt appetite and autonomic outflow.
“Although GRs are ubiquitously expressed in the brain, they are most abundant in the PVN and the hippocampus. In contrast, MR expression appears mostly confined to a few limbic sites regulating salt appetite and autonomic outflow (70, 71).”
From The HPA – Immune Axis and the Immunomodulatory Actions of Glucocorticoids in the Brain (2014) · cites this paper as [70]
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Towards an Evolutionary Theory of Stress Responses
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- Authors
- Joëls, M., Karst, H., DeRijk, R., & de Kloet, E. R.
- Affiliations
- University of Amsterdam (NL)
- Leiden University (NL)
- Corresponding author
- Joëls, Marian
- Venue
- Trends in Neurosciences
- Publisher
- Elsevier BV
- Published
- 2008-01
- Volume
- 31
- Issue
- 1
- Pages
- 1-7
- ISSN
- 0166-2236 (ISSN-L)
- OpenAlex
- W2148731425
- Cited by
- 481
- References
- 55
- Citations by year
- 2026: 3 · 2025: 10 · 2024: 16 · 2023: 13 · 2022: 16 · 2021: 24 · 2020: 16 · 2019: 29 · 2018: 26 · 2017: 32 · 2016: 47 · 2015: 30 · 2014: 41 · 2013: 36 · 2012: 32
- FWCI
- 1.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Trends in Neurosciences (publishedVersion)
- PubMed (publishedVersion)
- UvA-DARE (University of Amsterdam) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Koninklijke Nederlandse Akademie van Wetenschappen
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- 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
- mineralocorticoid receptor, glucocorticoid receptor, corticosteroids, stress response, limbic system, genetic variants, psychological stress
- MeSH terms
- Animals, Brain Chemistry, Humans, Stress, Psychological, Receptors, Mineralocorticoid
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