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Corticosteroid hormones in the central stress response: Quick-and-slow
Abstract
Recent evidence shows that corticosteroid hormones exert rapid non-genomic effects on neurons in the hypothalamus and the hippocampal CA1 region. The latter depend on classical mineralocorticoid receptors which are accessible from the outside of the plasma membrane and display a 10-fold lower affinity for corticosterone than the nuclear version involved in neuroprotection. Consequently, this 'membrane' receptor could play an important role while corticosteroid levels are high, i.e. during the initial phase of the stress response. We propose that during this phase corticosterone promotes hippocampal excitability and amplifies the effect of other stress hormones. These permissive non-genomic effects may contribute to fast behavioral effects and encoding of stress-related information. The fast effects are complemented by slower glucocorticoid receptor-mediated effects which facilitate suppression of temporary raised excitability, recovery from the stressful experience and storage of information for future use.
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“Forebrain GR activation inhibits HPA activity through tonic negative-feedback inhibition.123,124”
From Early life adversity and the epigenetic programming of hypothalamic-pituitary-adrenal function (2014) · cites this paper as [123]
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Metadata
- Authors
- de Kloet, E. R., Karst, H., & Joëls, M.
- Affiliations
- Leiden University Medical Center (NL)
- University of Amsterdam (NL)
- Venue
- Frontiers in Neuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2008-05
- Volume
- 29
- Issue
- 2
- Pages
- 268-272
- ISSN
- 0091-3022 (ISSN-L)
- OpenAlex
- W2137942121
- Cited by
- 391
- References
- 43
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 7 · 2023: 11 · 2022: 17 · 2021: 16 · 2020: 21 · 2019: 14 · 2018: 25 · 2017: 17 · 2016: 27 · 2015: 23 · 2014: 38 · 2013: 22 · 2012: 31
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Frontiers in Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- UvA-DARE (University of Amsterdam) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Life Sciences › Neuroscience › Cognitive Neuroscience › Memory and Neural Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- corticosteroids, non-genomic steroid effects, glucocorticoid receptor, hypothalamus, hippocampal CA1, hippocampal excitability, stress response, corticosterone, neuroprotection
- MeSH terms
- Adrenal Cortex Hormones, Animals, Hippocampus, Humans, Hypothalamus, Neurons, Receptors, Glucocorticoid, Stress, Physiological, Time Factors, Genome, Receptors, Mineralocorticoid
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