Endogenous melatonin provides an effective circadian message to both the suprachiasmatic nuclei and the pars tuberalis of the rat.
The suprachiasmatic nuclei (SCN) distribute the circadian neural message to the pineal gland which transforms it into a humoral circadian message, the nocturnal melatonin synthesis, which in turn modulates tissues expressing melatonin receptors such as the SCN or the pars tuberalis (PT). Nuclear orphan receptors (NOR), including rorbeta and rev-erbalpha, have been presented as functional links between the positive and negative loops of the molecular clock. Recent findings suggest that these NOR could be the initial targets of melatonin's chronobiotic message within the SCN. We investigated the role of these NOR in the physiological effect of endogenous melatonin on these tissues. We monitored rorbeta and rev-erbalpha mRNA expression levels by quantitative in situ hybridization after pinealectomy. Pinealectomy had no effect on NOR circadian expression rhythms in the SCN in 8-day pinealectomized (PX) animals. However in animals PX for 3 months, significant desynchronization between per1 and per2 transcription patterns appeared. These results suggest that endogenous melatonin could sustain the circadian rhythmicity and the phase relationship between the molecular partners of the SCN circadian system on a long-term basis. On the other hand, pinealectomy decreased the level and abolished the rhythmicity of NOR mRNA expression in the PT. These effects were partially prevented by daily melatonin administration in the drinking water. These results show that NOR can be regulated by the melatonin circadian rhythm in the PT and could be the link between the physiological action of melatonin and the core of the molecular circadian clock in this tissue.
Agez
Laurence
L
Institut des Neurosciences Cellulaires et Intégratives, CNRS UMR 7168, Université Louis Pasteur, Strasbourg, France.
Laurent
Virginie
V
Guerrero
Hilda Y
HY
Pévet
Paul
P
Masson-Pévet
Mireille
M
Gauer
François
F
D000704:Analysis of Variance; D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D017403:In Situ Hybridization; D016018:Least-Squares Analysis; D016014:Linear Models; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism*; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000235:genetics / Q000378:metabolism; D056950:Period Circadian Proteins / Q000235:genetics / Q000378:metabolism; D010870:Pineal Gland / Q000601:surgery; D010903:Pituitary Gland, Anterior / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013493:Suprachiasmatic Nucleus / Q000378:metabolism*
C498263:Nr1d1 protein, rat; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1; C539024:Per1 protein, rat; C513311:Per2 protein, rat; D056950:Period Circadian Proteins; D008550:Melatonin