Genomic and epigenomic mechanisms of glucocorticoids in the brain
Abstract
Following the discovery of glucocorticoid receptors in the hippocampus and other brain regions, research has focused on understanding the effects of glucocorticoids in the brain and their role in regulating emotion and cognition. Glucocorticoids are essential for adaptation to stressors (allostasis) and in maladaptation resulting from allostatic load and overload. Allostatic overload, which can occur during chronic stress, can reshape the hypothalamic-pituitary-adrenal axis through epigenetic modification of genes in the hippocampus, hypothalamus and other stress-responsive brain regions. Glucocorticoids exert their effects on the brain through genomic mechanisms that involve both glucocorticoid receptors and mineralocorticoid receptors directly binding to DNA, as well as by non-genomic mechanisms. Furthermore, glucocorticoids synergize both genomically and non-genomically with neurotransmitters, neurotrophic factors, sex hormones and other stress mediators to shape an organism's present and future responses to a stressful environment. Here, we discuss the mechanisms of glucocorticoid action in the brain and review how glucocorticoids interact with stress mediators in the context of allostasis, allostatic load and stress-induced neuroplasticity.
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Under prolonged exposure to negative environmental stressors, high concentrations of glucocorticoids produced along HPA axis lead to overactivation of GR in CNS target cells.
“Under prolonged exposure to negative environmental stressors, high concentrations of glucocorticoids produced along the HPA axis led to the overactivation of glucocorticoid receptors (GR) in central nervous system target cells”
From Serum/glucocorticoid regulated kinase 1 (SGK1) in neurological disorders: pain or gain (2024) · cites this paper as Gray et al., 2017
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- Authors
- Gray, J. D., Kogan, J. F., Marrocco, J., & McEwen, B. S.
- Affiliations
- Rockefeller University (US)
- Corresponding author
- McEwen, Bruce S.
- Venue
- Nature Reviews Endocrinology
- Published
- 2017-09-01
- Volume
- 13
- Issue
- 11
- Pages
- 661-673
- ISSN
- 1759-5029 (ISSN-L)
- 1759-5037
- OpenAlex
- W2751708584
- Cited by
- 242
- References
- 36
- Citations by year
- 2026: 17 · 2025: 21 · 2024: 39 · 2023: 34 · 2022: 20 · 2021: 28 · 2020: 31 · 2019: 38 · 2018: 13 · 2017: 1
- FWCI
- 2.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Reviews Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- 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
- glucocorticoids, glucocorticoid receptor, mineralocorticoid receptor, allostasis, allostatic load, allostatic overload, chronic stress, hypothalamic-pituitary-adrenal axis, hippocampus, epigenetic modifications, stress-induced neuroplasticity, emotion regulation, cognition, sex hormones, neurotransmitters, neurotrophic factors
- MeSH terms
- Adaptation, Physiological, Animals, Mental Disorders, Brain, Gene Expression Regulation, Glucocorticoids, Humans, Hypothalamo-Hypophyseal System, Neuronal Plasticity, Pituitary-Adrenal System, Receptors, Glucocorticoid, Sex Factors, Stress, Physiological, Stress, Psychological, Receptors, Mineralocorticoid, Genomics, Allostasis, Epigenomics
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