Circadian clocks: regulators of endocrine and metabolic rhythms
Abstract
Daily and seasonal rhythms in the endocrine system are co-ordinated by a hypothalamic pacemaker, the suprachiasmatic nuclei (SCN) that is synchronised to solar time by direct retinal afferents. Individual SCN neurons are circadian clocks, their intrinsic oscillator consisting of a series of interlinked autoregulatory transcriptional/post-translational feedback loops incorporating Period ( Per ) and Cryptochrome ( Cry ) genes. Mutations that alter the rate of transcription of Per and Cry genes or the stability of Per and Cry proteins affect clock speed. Molecular timekeeping in SCN neurons is synchronised and sustained by interneuronal neuropeptidergic signals. A molecular clock mechanism comparable to that of the SCN is present in most major organ systems. These tissue clocks are synchronised by endocrine, autonomic and behavioural cues that are dependent on the SCN, and in turn they drive the circadian expression of local transcriptomes, thereby co-ordinating circadian metabolism and physiology. Rhythmic glucocorticoid signalling is a prominent mediator of SCN output and internal synchroniser. The role of local SCN-synchronised clocks in controlling vital processes, including xenobiotic detoxification, cell division and nutrient metabolism, is essential to health, and disturbances to circadian timing arising from modern working schedules are becoming recognised as an increasingly relevant factor in major systemic illness. Moreover, the newly identified molecular components of circadian control systems provide novel avenues for therapeutic intervention.
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The normal function of the circadian system is based on a hierarchical network of central and peripheral clocks.
“The normal function of the circadian system is based on a hierarchical network of central and peripheral clocks [224].”
From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [224]
This complex interconnected regulatory framework ensures that the same molecules that regulate metabolism and reproduction also contribute to a bidirectional feedback system with the autonomous circadian circuits, resulting in synchronicity of internal physiology with environmental cues to optimize both individual and species survival.
“This complex interconnected regulatory framework, ensures that the same molecules that regulate metabolism and reproduction, also contribute to a bidirectional feedback system with the autonomous circadian circuits [224,231]. This results in synchronicity of internal physiology with environmental cues, to optimize both individual and species survival.”
From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [224]
The central clock can convey rhythmic information to peripheral clocks in other tissues and organs throughout the body.
“The central clock can then convey rhythmic information to peripheral clocks in other tissues and organs throughout the body [224].”
From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [224]
Circadian rhythms are generated by the endogenous master pacemaker in the suprachiasmatic nucleus and are entrained by environmental timing cues, most importantly light signaled via the retinohypothalamic tract.
“Circadian rhythms are generated by the endogenous master pacemaker located in the paired suprachiasmatic nucleus (SCN) of the hypothalamus and are kept entrained to the local conditions by environmental timing cues; the most important of these cues is light, that signaled to the SCN by direct input from the retina via the retinohypothalamic tract [1].”
From Impact of Sleep and Its Disturbances on Hypothalamo-Pituitary-Adrenal Axis Activity (2010) · cites this paper as [1]
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BackgroundCircadian clock protein BMAL1 regulates IL-1β in macrophages via NRF2
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“The alternating activation and suppression of the BMAL1-driven positive loop and the PER/CRY-controlled negative loop result in a circadian oscillation of the molecular clock [16,17,18].”
BackgroundRegulation of Clock-Controlled Genes in Mammals
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Stress, Endocrine Physiology and Pathophysiology -- Endotext
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Maternal Feeding Controls Fetal Biological Clock
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Kandeğer, A., Eğilmez, Ü., Sayin, A. A., & Selvı, Y. (2018) · Psychiatry Research · doi:10.1016/j.psychres.2018.08.003 · Cited by 63 · see citing works
Sirtuin-dependent clock control
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Altered expression patterns of clock gene mRNAs and clock proteins in human skin tumors
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Aging of Intrinsic Circadian Rhythms and Sleep in a Diurnal Nonhuman Primate, Macaca mulatta
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Leptin Modulates Spike Coding in the Rat Suprachiasmatic Nucleus
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Seasonal changes in mood and behavior are linked to metabolic syndrome
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Fibroblast PER2 Circadian Rhythmicity Depends on Cell Density
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Genetic association study of circadian genes with seasonal pattern in bipolar disorders
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Basic Concepts and Hormonal Regulators of the Stress System
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Approaches to the Pharmacological Management of Jet Lag
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Dual-Color Luciferase Mouse Directly Demonstrates Coupled Expression of Two Clock Genes
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- Authors
- Hastings, M., O’Neill, J. S., & Maywood, E. S.
- Affiliations
- MRC Laboratory of Molecular Biology (GB)
- Venue
- Journal of Endocrinology
- Publisher
- Bioscientifica
- Published
- 2007-11
- Volume
- 195
- Issue
- 2
- Pages
- 187-198
- ISSN
- 0022-0795 (ISSN-L)
- 1479-6805
- OpenAlex
- W2149487034
- Cited by
- 426
- References
- 109
- Citations by year
- 2026: 9 · 2025: 10 · 2024: 13 · 2023: 19 · 2022: 19 · 2021: 30 · 2020: 22 · 2019: 11 · 2018: 29 · 2017: 27 · 2016: 24 · 2015: 26 · 2014: 23 · 2013: 22 · 2012: 23
- FWCI
- 12.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Directorate for Biological Sciences
- Medical Research Council
- Biotechnology and Biological Sciences Research Council
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- circadian clock, suprachiasmatic nucleus, endocrine rhythms, metabolic rhythms, period gene, transcriptional feedback loop, glucocorticoid signaling, circadian metabolism, circadian rhythm disruption, shift work, xenobiotic detoxification, cell division, nutrient metabolism
- MeSH terms
- Animals, Biological Clocks, Circadian Rhythm, Computer Systems, Endocrine Glands, Fluorescent Dyes, Health, Humans, Light, Neural Pathways, Periodicity, Suprachiasmatic Nucleus, Signal Transduction
About these checks
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