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The Functional and Clinical Significance of the 24-Hour Rhythm of Circulating Glucocorticoids
Open accessAbstract
Adrenal glucocorticoids are major modulators of multiple functions, including energy metabolism, stress responses, immunity, and cognition. The endogenous secretion of glucocorticoids is normally characterized by a prominent and robust circadian (around 24 hours) oscillation, with a daily peak around the time of the habitual sleep-wake transition and minimal levels in the evening and early part of the night. It has long been recognized that this 24-hour rhythm partly reflects the activity of a master circadian pacemaker located in the suprachiasmatic nucleus of the hypothalamus. In the past decade, secondary circadian clocks based on the same molecular machinery as the central master pacemaker were found in other brain areas as well as in most peripheral tissues, including the adrenal glands. Evidence is rapidly accumulating to indicate that misalignment between central and peripheral clocks has a host of adverse effects. The robust rhythm in circulating glucocorticoid levels has been recognized as a major internal synchronizer of the circadian system. The present review examines the scientific foundation of these novel advances and their implications for health and disease prevention and treatment.
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“This rhythm is important for its action because cortisol, not melatonin, is recognized to be the key metabolic central synchronizing signal [60–62].”
From Sleep, testosterone and cortisol balance, and ageing men (2022) · cites this paper as [60]
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“Experimental administration of glucocorticoid synchronizes the peripheral clocks located in liver, muscle, and adipose tissue which are the major storage sites for glycogen, protein, and fat, respectively, as well as other metabolically relevant organs such as pancreas and gut [60–63].”
From Sleep, testosterone and cortisol balance, and ageing men (2022) · cites this paper as [60]
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“These findings are highly relevant because hypercortisolemia during the late-afternoon and early-evening is harmful, and is believed to cause the insulin resistance observed with advanced age [60, 69, 70], impair physical performance [71] and trigger neurocognitive deficits [72].”
From Sleep, testosterone and cortisol balance, and ageing men (2022) · cites this paper as [60]
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“Disruption of these hormone rhythms often leads to disease ( 2 ),”
From Dynamic modulation of glucose utilisation by glucocorticoid rhythms in health and disease (2020) · cites this paper as [2]
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“in hypercortisolism, it is not only that CORT levels are higher than normal, but in some cases, they also display abnormal rhythmicity. This varies depending on whether the underlying condition is associated with Cushing's syndrome, depression, PTSD, acute inflammation following major surgery, or chronic inflammatory diseases (e.g., rheumatoid arthritis) ( 2, 5-13, 57-60 ).”
From Dynamic modulation of glucose utilisation by glucocorticoid rhythms in health and disease (2020) · cites this paper as [2]
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“many of these conditions are accompanied by a disruption of normal glucose metabolism while preserving some degree of CORT rhythmicity.”
From Dynamic modulation of glucose utilisation by glucocorticoid rhythms in health and disease (2020) · cites this paper as [2]
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“Similarly, mounting evidence suggests that circadian clock genes within the brain, skeletal muscle, adipose tissue, gut, liver and pancreas (to name a few) may play a major role in regulating insulin sensitivity, possibly cooperating with glucocorticoids in controlling circadian variability ( 2, 73, 74 ).”
From Dynamic modulation of glucose utilisation by glucocorticoid rhythms in health and disease (2020) · cites this paper as [2]
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Metadata
- Authors
- Oster, H., Challet, E., Ott, V., Arvat, E., de Kloet, E. R., Dijk, D.-J., Lightman, S., Vgontzas, A., & Van Cauter, E.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Medical Department I (H.O., V.O.), University of Lübeck, 23562 Lübeck, Germany; Institute for Cellular and Integrative Neuroscience (E.C.), Centre National de la Recherche Scientifique (CNRS) UPR 3212, University of Strasbourg, 67084 Strasbourg, France; Division of Endocrinology, Diabetology and Metabolism (E.A.), Department of Internal Medicine, University of Turin, 10043 Turin, Italy; Departmen
- ORCID
- Venue
- Endocrine Reviews
- Publisher
- The Endocrine Society
- Published
- 2016-10-17
- Volume
- 38
- Issue
- 1
- Pages
- 3-45
- ISSN
- 0163-769X (ISSN-L)
- 1945-7189
- PMC
- PMC5563520
- OpenAlex
- W2535896286
- Cited by
- 548
- References
- 440
- Citations by year
- 2026: 64 · 2025: 77 · 2024: 47 · 2023: 61 · 2022: 57 · 2021: 72 · 2020: 77 · 2019: 35 · 2018: 31 · 2017: 24 · 2016: 1
- FWCI
- 3.21
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Endocrine Reviews (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Explore Bristol Research (publishedVersion, cc-by)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- HAL (submittedVersion, other-oa)
- Leiden Repository (Leiden University) (submittedVersion)
- Institutional Research Information System University of Turin (University of Turin) (submittedVersion)
- Bristol Research (University of Bristol) (submittedVersion, cc-by)
- Funders
- Medical Research Council (MR/J008893/1, MR/J012548/1)
- Biotechnology and Biological Sciences Research Council (BB/L007622/1)
- 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 rhythm, circadian clock, suprachiasmatic nucleus, adrenal gland, peripheral circadian clock, sleep-wake transition, circadian misalignment, adrenal steroid secretion
- MeSH terms
- Animals, Circadian Rhythm, Glucocorticoids, Humans, Circadian Clocks
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