Resetting of circadian time in peripheral tissues by glucocorticoid signaling.
In mammals, circadian oscillators reside not only in the suprachiasmatic nucleus of the brain, which harbors the central pacemaker, but also in most peripheral tissues. Here, we show that the glucocorticoid hormone analog dexamethasone induces circadian gene expression in cultured rat-1 fibroblasts and transiently changes the phase of circadian gene expression in liver, kidney, and heart. However, dexamethasone does not affect cyclic gene expression in neurons of the suprachiasmatic nucleus. This enabled us to establish an apparent phase-shift response curve specifically for peripheral clocks in intact animals. In contrast to the central clock, circadian oscillators in peripheral tissues appear to remain responsive to phase resetting throughout the day.
Balsalobre
A
A
Département de Biologie Moléculaire, Sciences II, Université de Genève, 30 Quai Ernest Ansermet, CH-1211 Genève, Switzerland.
Brown
S A
SA
Marcacci
L
L
Tronche
F
F
Kellendonk
C
C
Reichardt
H M
HM
Schütz
G
G
Schibler
U
U
D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D018797:Cell Cycle Proteins; D002460:Cell Line; D002940:Circadian Rhythm / Q000502:physiology*; D004268:DNA-Binding Proteins; D003907:Dexamethasone / Q000031:analogs & derivatives / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009154:Mutation; D009206:Myocardium / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D056950:Period Circadian Proteins; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D013493:Suprachiasmatic Nucleus / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
D018797:Cell Cycle Proteins; C485975:DBP protein, rat; D004268:DNA-Binding Proteins; C498260:Dbp protein, mouse; D009687:Nuclear Proteins; C539023:Per1 protein, mouse; C539024:Per1 protein, rat; D056950:Period Circadian Proteins; D011965:Receptors, Glucocorticoid; D014157:Transcription Factors; C004180:dexamethasone 21-phosphate; D003907:Dexamethasone