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The adrenal peripheral clock: Glucocorticoid and the circadian timing system
Abstract
The mammalian circadian timing system is organized in a hierarchy, with the master clock residing in the suprachiasmatic nucleus (SCN) of the hypothalamus and subsidiary peripheral clocks in other brain regions as well as peripheral tissues. Since the local oscillators in most cells contain a similar molecular makeup to that in the central pacemaker, determining the role of the peripheral clocks in the regulation of rhythmic physiology and behavior is an important issue. Glucocorticoids (GCs) are a class of multi-functional adrenal steroid hormones, which exhibit a robust circadian rhythm, with a peak linked with the onset of the daily activity phase. It has long been believed that the production and secretion of GC is primarily governed through the hypothalamus-pituitary-adrenal (HPA) neuroendocrine axis in mammals. Growing evidence, however, strongly supports the notion that the periodicity of GC involves the integrated activity of multiple regulatory mechanisms related to circadian timing system along with the classical HPA neuroendocrine regulation. The adrenal-intrinsic oscillator as well as the central pacemaker plays a pivotal role in its rhythmicity. GC influences numerous biological processes, such as metabolic, cardiovascular, immune and even higher brain functions, and also acts as a resetting signal for the ubiquitous peripheral clocks, suggesting its importance in harmonizing circadian physiology and behavior. In this review, we will therefore focus on the recent advances in our understanding of the circadian regulation of adrenal GC and its functional relevance.
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“the circadian system regulates glucocorticoid secretion from the adrenal glands, such that concentrations tend to peak in the morning just before awakening and decrease throughout the day in diurnal animals, including humans52,53.”
From Circadian rhythm disruption and mental health (2020) · cites this paper as [52]
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The sweet tooth of the circadian clock
Fu, M., & Yang, X. (2017) · Biochemical Society Transactions · doi:10.1042/bst20160183 · Cited by 11
Potential for the development of light therapies in mild traumatic brain injury
Raikes, A. C., & Killgore, W. D. S. (2018) · Concussion · doi:10.2217/cnc-2018-0006 · Cited by 13
“Among these, glucocorticoids like cortisol exhibit circadian rhythmicity, with a nighttime accumulation period and clearance during the day [187,188].”
BackgroundFrahm, K., Williams, A. A., Wood, A. N., Ewing, M., Mattila, P. E., Chuan, B. W., Guo, L., Shah, F. A., O'Donnell, C. P., Lu, R., et al. (2020) · Endocrinology · doi:10.1210/endocr/bqaa163 · Cited by 11
Dilixiati, A., Koyanagi, S., Kusunose, N., Matsunaga, N., & Ohdo, S. (2017) · Journal of Pharmacological Sciences · doi:10.1016/j.jphs.2017.07.004 · Cited by 10
Effect of Cage Space on Behavior and Reproduction in Crl:CD(SD) and BN/Crl Laboratory Rats.
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Noncoding RNAs: Bridging Regulation of Circadian Rhythms and Inflammation
Hardeland, R. (2019) · Advances in Neuroimmune Biology · doi:10.3233/nib-190159 · Cited by 9
Corticosteroids and circadian rhythms in the cardiovascular system
Kanki, M., & Young, M. J. (2020) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2020.10.007 · Cited by 9
Sleep and Circadian Rhythm Disruption in Psychosis
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“Moreover, glucocorticoid effects on the limbic system are regulated by CRF, a promoter of the HPA axis, and HPA axis activation affects numerous surrounding target organs (29,38,39).”
Son, G. H., Chung, S., Ramirez, V. D., & Kim, K. (2016) · Medicinal Chemistry · doi:10.4172/2161-0444.1000421 · Cited by 8
Self-citationSpulber, S. D., Conti, M., Elberling, F., Raciti, M., Borroto‐Escuela, D. O., Fuxé, K., & Ceccatelli, S. (2019) · Translational Psychiatry · doi:10.1038/s41398-019-0594-3 · Cited by 8
Irradiation with X-rays phase-advances the molecular clockwork in liver, adrenal gland and pancreas
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“The phase-shifting effect of glucocorticoids is well known and has been described for many cells and tissues (Balsalobre et al., 2000; Kiessling et al., 2010; Pezük et al., 2012; Son et al., 2011).”
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“The circadian rhythmicity in their production with the minimal production in the morning and maximum in the evening is well documented [20].”
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“Interestingly, even if HPA axis activity is regulated by the master clock, ACTH is secreted in a lower amplitude manner compared to cortisol [12].”
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Is the Circadian Rhythm Dysregulation a Core Pathogenetic Mechanism of Bipolar Disorder?
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Circadian Rhythm: Light-Dark Cycles
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Metadata
- Authors
- Son, G. H., Chung, S., & Kim, K.
- Affiliations
- Seoul National University (KR)
- Corresponding author
- Kim, Kyungjin
- Venue
- Frontiers in Neuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2011-10
- Volume
- 32
- Issue
- 4
- Pages
- 451-465
- ISSN
- 0091-3022 (ISSN-L)
- OpenAlex
- W1971407944
- Cited by
- 136
- References
- 221
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 9 · 2023: 6 · 2022: 6 · 2021: 8 · 2020: 7 · 2019: 8 · 2018: 10 · 2017: 16 · 2016: 8 · 2015: 12 · 2014: 12 · 2013: 12 · 2012: 13
- FWCI
- 1.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Frontiers in Neuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- glucocorticoids, circadian system, peripheral clocks, adrenal gland, suprachiasmatic nucleus, hypothalamic-pituitary-adrenal axis, circadian rhythm, glucocorticoid secretion, clock resetting, circadian physiology
- MeSH terms
- Adrenal Glands, Animals, Biological Clocks, Glucocorticoids, Humans, Models, Biological, Signal Transduction, Neuroendocrine Cells, Circadian Clocks
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