Brain corticosteroid receptor balance in health and disease
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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An equivalent of hGR-β has yet to be described in other species, including mice and rats.
“an equivalent of hGR-β has yet to be described in other species, including mice and rats.77,78”
From Cytokines and Glucocorticoid Receptor Signaling (2009) · cites this paper as [78]
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- Authors
- 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)
- OpenAlex
- W2171238991
- Cited by
- 2,614
- References
- 0
- Citations by year
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- FWCI
- 8.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Endocrine Reviews (publishedVersion)
- PubMed (publishedVersion)
- UvA-DARE (University of Amsterdam) (publishedVersion)
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- 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 › Genetics › 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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