Stress, the Stress System and the Role of Glucocorticoids
Abstract
All living organisms have developed a highly conserved and regulatory system, the stress system, to cope with a broad spectrum of stressful stimuli that threaten, or are perceived as threatening, their dynamic equilibrium or homeostasis. This neuroendocrine system consists of the hypothalamic-pituitary-adrenal (HPA) axis and the locus caeruleus/norepinephrine-autonomic nervous system. In parallel with the evolution of the homeostasis and stress concepts from ancient Greek to modern medicine, significant advances in the field of neuroendocrinology have identified the physiologic biochemical effector molecules of the stress response. Glucocorticoids, the end-products of the HPA axis, play a fundamental role in the maintenance of both resting and stress-related homeostasis and, undoubtedly, influence the physiologic adaptive reaction of the organism against stressors. If the stress response is dysregulated in terms of magnitude and/or duration, homeostasis is turned into cacostasis with adverse effects on many vital physiologic functions, such as growth, development, metabolism, circulation, reproduction, immune response, cognition and behavior. A strong and/or long-lasting stressor may precipitate and/or cause many acute and chronic diseases. Moreover, stressors during pre-natal, post-natal or pubertal life may have a critical impact on our expressed genome. This review describes the central and peripheral components of the stress system, provides a comprehensive overview of the stress response, and discusses the role of glucocorticoids in a broad spectrum of stress-related diseases.
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Psychological stress activates the HPA axis, leading to secretion of glucocorticoid into the bloodstream, where blood glucocorticoid enters the brain through the BBB to activate GR and MR.
“Psychological stress activates the hypothalamic-pituitary-adrenocortical (HPA) axis, eventually leading to the secretion of glucocorticoid into the bloodstream, where blood glucocorticoid enters the brain through the BBB to activate the glucocorticoid receptor (GR in human) and mineral corticosteroid receptor (MR in mice) [556, 557].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [556]
The activated GC-GRα complex maintains resting and stress-related homeostasis and shapes the organism's adaptive response to stressors.
“The activated glucocorticoid-glucocorticoid receptor-alpha (GC-GRα) complex plays a fundamental role in the maintenance of both resting and stress-related homeostasis and influences the physiologic adaptive reaction of the organism against stressors [2].”
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- Authors
- Nicolaides, N. C., Kyratzi, E., Lamprokostopoulou, A., Chrousos, G. P., & Charmandari, E.
- Affiliations
- National and Kapodistrian University of Athens (GR)
- Biomedical Research Foundation of the Academy of Athens (GR)
- Venue
- Neuroimmunomodulation
- Publisher
- S. Karger AG
- Published
- 2014-09-12
- Volume
- 22
- Issue
- 1-2
- Pages
- 6-19
- ISSN
- 1021-7401 (ISSN-L)
- 1423-0216
- OpenAlex
- W1966453802
- Cited by
- 477
- References
- 77
- Citations by year
- 2026: 32 · 2025: 45 · 2024: 47 · 2023: 55 · 2022: 49 · 2021: 56 · 2020: 46 · 2019: 29 · 2018: 35 · 2017: 39 · 2016: 31 · 2015: 12 · 2014: 1
- FWCI
- 2.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- NeuroImmunoModulation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Keywords
- stress response, stress system, glucocorticoids, hypothalamic-pituitary-adrenal axis, locus coeruleus, norepinephrine, autonomic nervous system, homeostasis, stress-related disorders, neuroendocrinology
- MeSH terms
- Animals, Glucocorticoids, Humans, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Stress, Psychological
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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