Glucocorticoids as entraining signals for peripheral circadian oscillators.
Mammalian circadian organization is governed by pacemaker neurons in the brain that communicate with oscillators in peripheral tissues. Adrenal glucocorticoids are important time-giving signals to peripheral circadian oscillators. We investigated the rhythm of Per1-luc expression in pineal, pituitary, salivary glands, liver, lung, kidney, cornea as well as suprachiasmatic nucleus from adrenalectomized and sham-operated rats kept under light-dark cycles, or exposed to single 6-h phase delays or advances of their light cycles. Adrenalectomy shifted the phases of Per1-luc in liver, kidney, and cornea and caused phase desynchrony and significant dampening in the rhythmicity of cornea. Treatment with hydrocortisone shifted the phases of Per1-luc in most of the tissues examined, even those that were not affected by adrenalectomy. The rhythm in cornea recovered in animals given hydrocortisone in vivo or when corneas were treated with dexamethasone in vitro. Adrenalectomy increased the rate of reentrainment after phase shifts in liver, kidney, cornea, pineal, lung, and suprachiasmatic nucleus but not in pituitary and salivary glands. Our data show that glucocorticoids act as strong entraining signals for peripheral circadian oscillators and may feed back on central oscillators as well.
Department of Biology, University of Virginia, Charlottesville, Virginia 22904-4328, USA.
Pinar
P
Pezük
Jennifer A
JA
Mohawk
Laura A
LA
Wang
Michael
M
Menaker
D000315:Adrenalectomy; D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D005938:Glucocorticoids / Q000378:metabolism / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D056950:Period Circadian Proteins / Q000235:genetics* / Q000378:metabolism; D010870:Pineal Gland / Q000187:drug effects / Q000378:metabolism*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic; D013493:Suprachiasmatic Nucleus / Q000187:drug effects / Q000378:metabolism*
D005938:Glucocorticoids; C539024:Per1 protein, rat; D056950:Period Circadian Proteins; D003907:Dexamethasone; D006854:Hydrocortisone