Cited by 2,614Stress Responses and CortisolNeuroscience and Neuropharmacology ResearchEstrogen and related hormone effects

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Brain Corticosteroid Receptor Balance in Health and Disease

de Kloet, E. R.·1998·Endocrine Reviews

DOI 10.1210/er.19.3.269

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Abstract

In this review, we have described the function of MR and GR in hippocampal neurons. The balance in actions mediated by the two corticosteroid receptor types in these neurons appears critical for neuronal excitability, stress responsiveness, and behavioral adaptation. Dysregulation of this MR/GR balance brings neurons in a vulnerable state with consequences for regulation of the stress response and enhanced vulnerability to disease in genetically predisposed individuals. The following specific inferences can be made on the basis of the currently available facts. 1. Corticosterone binds with high affinity to MRs predominantly localized in limbic brain (hippocampus) and with a 10-fold lower affinity to GRs that are widely distributed in brain. MRs are close to saturated with low basal concentrations of corticosterone, while high corticosterone concentrations during stress occupy both MRs and GRs. 2. The neuronal effects of corticosterone, mediated by MRs and GRs, are long-lasting, site-specific, and conditional. The action depends on cellular context, which is in part determined by other signals that can activate their own transcription factors interacting with MR and GR. These interactions provide an impressive diversity and complexity to corticosteroid modulation of gene expression. 3. Conditions of predominant MR activation, i.e., at the circadian trough at rest, are associated with the maintenance of excitability so that steady excitatory inputs to the hippocampal CA1 area r…

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Authors: de Kloet, E. R.
Affiliations: Leiden University (NL)
ORCID: de Kloet, E. R.
Venue: Endocrine Reviews
Publisher: The Endocrine Society
Published: 1998-06-01
Volume: 19
Issue: 3
Pages: 269-301
ISSN: 0163-769X (ISSN-L)
DOI: 10.1210/er.19.3.269
OpenAlex: W2171238991
Cited by: 2,614
References: 0
Citations by year: 2026: 11 · 2025: 38 · 2024: 53 · 2023: 60 · 2022: 69 · 2021: 74 · 2020: 78 · 2019: 70 · 2018: 60 · 2017: 90 · 2016: 86 · 2015: 99 · 2014: 139 · 2013: 128 · 2012: 132
FWCI: 8.65
Type: journal article
Language: en
Open access: closed
Locations: Endocrine Reviews (publishedVersion)
PubMed (publishedVersion)
UvA-DARE (University of Amsterdam) (publishedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
Funders: European Commission (BRST960179)
Nederlandse Organisatie voor Wetenschappelijk Onderzoek
Internationale Stichting Alzheimer Onderzoek
Topics: Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
Keywords: mineralocorticoid receptor, glucocorticoid receptor, corticosterone, hippocampal neurons, neuronal excitability, stress response, hypothalamic-pituitary-adrenal axis, paraventricular nucleus, GABAergic inhibition, adrenalectomy, circadian rhythm, gene expression regulation, neuroendocrine adaptation, limbic system
MeSH terms: Adrenal Cortex Hormones, Aging, Brain, Brain Diseases, Health, Humans, Receptors, Steroid, Stress, Physiological

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