Glucocorticoid-mediated Period2 induction delays the phase of circadian rhythm

Cheon, Solmi; Park, Noheon; Cho, Sehyung; Kim, Kyungjin

doi:10.1093/nar/gkt307

Cited by 99 publications

(84 citation statements)

References 69 publications

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“…FS caused a significant increase in RNA expression of Fkbp5, Per1, and Sgk1, which is consistent with their well-known responsiveness to glucocorticoids (17)(18)(19)(20). The hnRNA levels for Per1 and Sgk1 peaked at 30 min, whereas Fkbp5 hnRNA levels reached their maximal levels later at 60 min.…”

Section: Discussionsupporting

confidence: 80%

Acute stress enhances heterodimerization and binding of corticosteroid receptors at glucocorticoid target genes in the hippocampus

Mifsud

Reul

2016

Proc. Natl. Acad. Sci. U.S.A.

153

173

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A stressful event results in secretion of glucocorticoid hormones, which bind to mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) in the hippocampus to regulate cognitive and affective responses to the challenge. MRs are already highly occupied by low glucocorticoid levels under baseline conditions, whereas GRs only become substantially occupied by stress- or circadian-driven glucocorticoid levels. Currently, however, the binding of MRs and GRs to glucocorticoid-responsive elements (GREs) within hippocampal glucocorticoid target genes under such physiological conditions in vivo is unknown. We found that forced swim (FS) stress evoked increased hippocampal RNA expression levels of the glucocorticoid-responsive genes FK506-binding protein 5 (Fkbp5), Period 1 (Per1), and serum- and glucocorticoid-inducible kinase 1 (Sgk1). Chromatin immunoprecipitation (ChIP) analysis showed that this stressor caused substantial gene-dependent increases in GR binding and surprisingly, also MR binding to GREs within these genes. Different acute challenges, including novelty, restraint, and FS stress, produced distinct glucocorticoid responses but resulted in largely similar MR and GR binding to GREs. Sequential and tandem ChIP analyses showed that, after FS stress, MRs and GRs bind concomitantly to the same GRE sites within Fkbp5 and Per1 but not Sgk1. Thus, after stress, MRs and GRs seem to bind to GREs as homo- and/or heterodimers in a gene-dependent manner. MR binding to GREs at baseline seems to be restricted, whereas after stress, GR binding may facilitate cobinding of MR. This study reveals that the interaction of MRs and GRs with GREs within the genome constitutes an additional level of complexity in hippocampal glucocorticoid action beyond expectancies based on ligand–receptor interactions.

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Section: Discussionsupporting

confidence: 80%

Acute stress enhances heterodimerization and binding of corticosteroid receptors at glucocorticoid target genes in the hippocampus

Mifsud

Reul

2016

Proc. Natl. Acad. Sci. U.S.A.

153

173

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“…These results might indicate a differential responsiveness of the different elements of the hepatic circadian clock to the glucocorticoids. However, this could depend on the model employed, since it has shown the presence of a GRE in Cry1 gene in mice and humans (Reddy et al 2007), and a synchronization of Per2 gene by a glucocorticoid treatment (Cheon et al 2013).…”

Section: Discussionmentioning

confidence: 99%

Performing a hepatic timing signal: glucocorticoids induce gper1a and gper1b expression and repress gclock1a and gbmal1a in the liver of goldfish

et al. 2015

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Glucocorticoids have been recently proposed as input signals of circadian system, although the underlying molecular mechanism remains unclear. This work investigates the role of glucocorticoids as modulators of clock genes expression in the liver of goldfish. In fish maintained under a 12L:12D photoperiod, an intraperitoneal injection at Zeitgeber Time 2 of a glucocorticoid analog, dexamethasone (1 μg/g body weight) induced per1 genes while decreased gbmal1a and gclock1a expression in the liver at 8 h post-injection. A 4-h in vitro exposure of goldfish liver to cortisol (0.1-10 μM) also induced gper1 genes in a concentration-dependent manner. Similarly, the exposure of the goldfish cultured liver to dexamethasone produced a concentration-dependent induction of gper1 genes. Moreover, this glucocorticoid analog led to a decrease in gbmal1a and gclock1a transcripts, while the other clock genes analyzed were unaffected. The induction of gper1a and gper1b by dexamethasone in vitro was observed at short times (2 h), whereas the reductions of gbmal1a and gclock1a transcripts needed longer exposure times (8 h) to the glucocorticoid to be significant. Additionally, a 2-h exposure to dexamethasone in the liver culture was enough to extend the induction of per genes for more than 12 h. Present results indicate that gper1 genes are targets for glucocorticoids in the regulation of goldfish hepatic oscillator, as previously reported in mammals, suggesting a conserved role of glucocorticoids in the functional organization of the peripheral circadian system in vertebrates. The repression of clock1a and bmal1a is not so well established, and suggests that other clock genes could be glucocorticoid targets in the goldfish liver.

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“…Functional glucocorticoid response elements (GREs) in the promoter regions of Per1, Per2, and E4bp4 have also been reported as possible factors in the signaling mechanisms of molecular clocks [26, 27], and the expression of Rev - erbα in the liver has been reported to decrease in response to glucocorticoid treatment via GREs [28]. In our most recent study, we also confirmed that dexamethasone (an analog of corticosterone) induced phase entrainment of peripheral PER2 rhythms in the liver, kidney, and submandibular gland [20].…”

Section: Stress-induced Entrainment Of the Circadian Clockmentioning

confidence: 99%

The mammalian circadian clock and its entrainment by stress and exercise

2016

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The mammalian circadian clock regulates day–night fluctuations in various physiological processes. The circadian clock consists of the central clock in the suprachiasmatic nucleus of the hypothalamus and peripheral clocks in peripheral tissues. External environmental cues, including light/dark cycles, food intake, stress, and exercise, provide important information for adjusting clock phases. This review focuses on stress and exercise as potent entrainment signals for both central and peripheral clocks, especially in regard to the timing of stimuli, types of stressors/exercises, and differences in the responses of rodents and humans. We suggest that the common signaling pathways of clock entrainment by stress and exercise involve sympathetic nervous activation and glucocorticoid release. Furthermore, we demonstrate that physiological responses to stress and exercise depend on time of day. Therefore, using exercise to maintain the circadian clock at an appropriate phase and amplitude might be effective for preventing obesity, diabetes, and cardiovascular disease.

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Glucocorticoid-mediated Period2 induction delays the phase of circadian rhythm

Cited by 99 publications

References 69 publications

Acute stress enhances heterodimerization and binding of corticosteroid receptors at glucocorticoid target genes in the hippocampus

Acute stress enhances heterodimerization and binding of corticosteroid receptors at glucocorticoid target genes in the hippocampus

Performing a hepatic timing signal: glucocorticoids induce gper1a and gper1b expression and repress gclock1a and gbmal1a in the liver of goldfish

The mammalian circadian clock and its entrainment by stress and exercise

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