How nuclear receptors tell time

Laboratoire de Biologie et Physiopathologie des Systèmes Intégrés, Université de Nice Sophia Antipolis and Centre National de la Recherche Scientifique, Nice, France Submitted 14 May 2009 ; accepted in final form 23 July 2009 Most organisms adapt their behavior and physiology to the daily changes in...

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Published in:Journal of applied physiology (1985) 2009-12, Vol.107 (6), p.1965-1971
Main Authors: Teboul, Michele, Grechez-Cassiau, Aline, Guillaumond, Fabienne, Delaunay, Franck
Format: Article
Language:English
Subjects:
Animals
Circadian rhythm
Circadian Rhythm - genetics
Circadian Rhythm - physiology
CLOCK Proteins - genetics
CLOCK Proteins - physiology
Feedback, Physiological - physiology
Homeostasis - genetics
Homeostasis - physiology
Hormones
Humans
Mammals
Metabolic Networks and Pathways - genetics
Metabolic Networks and Pathways - physiology
Receptors, Cytoplasmic and Nuclear - genetics
Receptors, Cytoplasmic and Nuclear - physiology
Signal transduction
Studies
T cell receptors
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Summary:Laboratoire de Biologie et Physiopathologie des Systèmes Intégrés, Université de Nice Sophia Antipolis and Centre National de la Recherche Scientifique, Nice, France Submitted 14 May 2009 ; accepted in final form 23 July 2009 Most organisms adapt their behavior and physiology to the daily changes in their environment through internal ( 24 h) circadian clocks. In mammals, this time-keeping system is organized hierarchically, with a master clock located in the suprachiasmatic nuclei of the hypothalamus that is reset by light, and that, in turn, coordinates the oscillation of local clocks found in all cells. Central and peripheral clocks control, in a highly tissue-specific manner, hundreds of target genes, resulting in the circadian regulation of most physiological processes. A great deal of knowledge has accumulated during the last decade regarding the molecular basis of mammalian circadian clocks. These studies have collectively demonstrated how a set of clock genes and their protein products interact together in complex feedback transcriptional/translational loops to generate 24-h oscillations at the molecular, cellular, and organism levels. In recent years, a number of nuclear receptors (NRs) have been implicated as important regulators of the mammalian clock mechanism. REV-ERB and retinoid-related orphan receptor NRs regulate directly the core feedback loop and increase its robustness. The glucocorticoid receptor mediates the synchronizing effect of glucocorticoid hormones on peripheral clocks. Other NR family members, including the orphan NR EAR2, peroxisome proliferator activated receptors- / , estrogen receptor- , and retinoic acid receptors, are also linked to the clockwork mechanism. These findings together establish nuclear hormone receptor signaling as an integral part of the circadian timing system. circadian physiology; feedback loop; hormones Address for reprint requests and other correspondence: F. Delaunay, Université de Nice Sophia Antipolis, CNRS FRE 3094, 28 Av Valrose, Nice cedex 2, 06108 France (e-mail: delaunay{at}unice.fr ).
ISSN:8750-7587
1522-1601
DOI:10.1152/japplphysiol.00515.2009