Interactions of the circadian CLOCK system and the HPA axis

Unit on Molecular Hormone Action, Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Trends in Endocrinology and Metabolism (Impact Factor: 8.87). 05/2010; 21(5):277-86. DOI: 10.1016/j.tem.2009.12.011
Source: PubMed

ABSTRACT Organisms have developed concurrent behavioral and physiological adaptations to the strong influence of day/night cycles, as well as to unforeseen, random stress stimuli. These circadian and stress-related responses are achieved by two highly conserved and interrelated regulatory networks, the circadian CLOCK and stress systems, which respectively consist of oscillating molecular pacemakers, the Clock/Bmal1 transcription factors, and the hypothalamic-pituitary-adrenal (HPA) axis and its end-effector, the glucocorticoid receptor. These systems communicate with one another at different signaling levels and dysregulation of either system can lead to development of pathologic conditions. In this review, we summarize the mutual physiologic interactions between the circadian CLOCK system and the HPA axis, and discuss their clinical implications.

Download full-text


Available from: George Chrousos, Aug 28, 2015
    • "Glucocorticoids are mainly related to metabolism and the stress response (Aluru and Vijayan, 2007). The circulating levels of these hormones show a strong circadian rhythm in vertebrates, that seems to be driven by central and peripheral oscillators (Kalsbeek et al., 2012; Nader et al., 2010). Nevertheless, daily fluctuations in glucocorticoids have been suggested also as an input to the circadian system. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The circadian system drives daily physiological and behavioral rhythms that allow animals to anticipate cyclic environmental changes. The discovery of the known as "clock genes", which are very well conserved through vertebrate phylogeny, highlighted the molecular mechanism of circadian oscillators functioning, based on transcription and translation cycles (∼24 h) of such clock genes. Studies in goldfish have shown that the circadian system in this species is formed by a net of oscillators distributed at central and peripheral locations, as the retina, brain, gut and liver, among others. In this work we review the existing information about the hepatic oscillator in goldfish due to its relevance in metabolism, and its key role as target of a variety of humoral signals. Different input signals modify the molecular clockwork in the liver of goldfish. Among them, there are environmental cues (photocycle and feeding regime) and different encephalic and peripheral endogenous signals (orexin, ghrelin and glucocorticoids). Per clock genes seem to be a common target for different signals. Thus, this genes family might be important for shifting the hepatic oscillator. The physiological relevance of the crosstalking between metabolic and feeding-related hormones and the hepatic clock sets the stage for the hypothesis that these hormones could act as "internal zeitgebers" communicating oscillators in the goldfish circadian system. Copyright © 2015. Published by Elsevier Inc.
    General and Comparative Endocrinology 05/2015; DOI:10.1016/j.ygcen.2015.05.001 · 2.67 Impact Factor
  • Source
    • "ingly , an improvement in declarative memory with tDCS was only seen when tDCS was applied during sleep , thought to be an important brain state for consolidating declarative memories ( Marshall et al . , 2004 ) . Serum cortisol , which shows circadian variations across the day , is thought to have an impact on brain function and neuroplasticity ( Nader et al . , 2010 ) . It has recently been demonstrated that cortisol levels influence TMS - induced neuroplasticity ; higher cortisol levels predict greater response to a neuroplasticity protocol based on repetitive TMS ( Clow et al . , 2014 ) . In fact , TMS studies typically have paid particular attention to testing subjects at similar times of day , "
    [Show abstract] [Hide abstract]
    ABSTRACT: There has been an explosion of research using transcranial direct current stimulation (tDCS) for investigating and modulating human cognitive and motor function in healthy populations. It has also been used in many studies seeking to improve deficits in disease populations. With the slew of studies reporting " promising results " for everything from motor recovery after stroke to boosting memory function, one could be easily seduced by the idea of tDCS being the next panacea for all neurological ills. However, huge variability exists in the reported effects of tDCS, with great variability in the effect sizes and even contradictory results reported. In this review, we consider the interindividual factors that may contribute to this variability. In particular, we discuss the importance of baseline neuronal state and features, anatomy, age and the inherent variability in the injured brain. We additionally consider how interindividual variability affects the results of motor-evoked potential (MEP) testing with transcranial magnetic stimulation (TMS), which, in turn, can lead to apparent variability in response to tDCS in motor studies.
    Frontiers in Cellular Neuroscience 04/2015; 1(9). DOI:10.3389/fncel.2015.00181 · 4.18 Impact Factor
  • Source
    • "The HPA axis, through glucocorticoids, exerts influence on many important biological processes, and glucocorticoids are proposed to have an important synchronizing role on peripheral circadian rhythms [3] [63]. Glucocorticoids have been found to broadly influence gene expression through GR [64]. When activated, the cytoplasmic GR, previously in an inactive complexed state, undergoes conformational changes and, after dimerization, translocates into the nucleus. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Many physiological processes and most endocrine functions show fluctuations over the course of the day. These so-called circadian rhythms are governed by an endogenous network of cellular clocks and serve as an adaptation to daily and, thus, predictable changes in the organism’s environment. Circadian clocks have been described in several tissues of the stress axis and in adipose cells where they regulate the rhythmic and stimulated release of stress hormones, such as glucocorticoids, and various adipokine factors. Recent work suggests that both adipose and stress axis clock systems reciprocally influence each other and adrenal-adipose rhythms may be key players in the development and therapy of metabolic disorders. In this review, we summarize our current understanding of adrenal and adipose tissue rhythms and clocks and how they might interact to regulate energy homoeostasis and stress responses under physiological conditions. Potential chronotherapeutic strategies for the treatment of metabolic and stress disorders are discussed.
    International Journal of Endocrinology 01/2015; 2015:1-13. DOI:10.1155/2015/693204 · 1.52 Impact Factor
Show more