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Circadian endocrine rhythms: the hypothalamic–pituitary–adrenal axis and its actions
Open accessAbstract
The stress system effectively restores the internal balance—or homeostasis—of living organisms in the face of random external or internal changes, the stressors. This highly complex system helps organisms to provide a series of neuroendocrine responses to stressors—the stress response—through coordinated activation of the hypothalamic–pituitary–adrenal (HPA) axis and the locus coeruleus/norepinephrine autonomic nervous systems. In addition to stressors, life is influenced by daily light/dark changes due to the 24‐h rotation of Earth. To adjust to these recurrent day/night cycles, the biological clock system employs the heterodimer of transcription factors circadian locomotor output cycle kaput/brain–muscle–arnt–like protein 1 (CLOCK/BMAL1), along with a set of other transcription factors, to regulate the circadian pattern of gene expression. Interestingly, the stress system, through the HPA axis, communicates with the clock system; therefore, any uncoupling or dysregulation could potentially cause several disorders, such as metabolic, autoimmune, and mood disorders. In this review, we discuss the biological function of the two systems, their interactions, and the clinical implications of their dysregulation or uncoupling.
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“These pathways are tightly and bi-directionally linked with HPA axis activity (Lee et al. 2013;Nicolaides et al. 2014)”
From The HPA axis in bipolar disorder: Systematic review and meta-analysis (2016) · cites this paper as Nicolaides et al. 2014
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Background
Metadata
- Authors
- Nicolaides, N. C., Charmandari, E., Chrousos, G. P., & Kino, T.
- Affiliations
- National and Kapodistrian University of Athens (GR)
- King Abdulaziz University (SA)
- National Institutes of Health (US)
- Corresponding author
- Nicolaides, Nicolas C.
- Venue
- Annals of the New York Academy of Sciences
- Publisher
- Wiley
- Published
- 2014-05
- Volume
- 1318
- Issue
- 1
- Pages
- 71-80
- ISSN
- 0077-8923 (ISSN-L)
- 1749-6632
- PMC
- PMC4104011
- OpenAlex
- W1598021542
- Cited by
- 183
- References
- 78
- Citations by year
- 2026: 11 · 2025: 17 · 2024: 15 · 2023: 16 · 2022: 12 · 2021: 16 · 2020: 18 · 2019: 12 · 2018: 13 · 2017: 14 · 2016: 20 · 2015: 17 · 2014: 2
- FWCI
- 2.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of the New York Academy of Sciences (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (ZIAHD008732)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Keywords
- circadian rhythm, hypothalamic-pituitary-adrenal axis, stress response, biological clock, Clock/BMAL1, circadian gene expression, circadian dysfunction, metabolic disorders, autoimmune disease, mood disorders
- MeSH terms
- Animals, Circadian Rhythm, Gene Expression Regulation, Glucocorticoids, Humans, Hypothalamo-Hypophyseal System, Pituitary-Adrenal System, Receptors, Glucocorticoid, CLOCK Proteins, ARNTL Transcription Factors
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