title: A noradrenergic sensitive endogenous clock is present in the rat pineal gland.
abstract: The aim of this study was to examine the occurrence of endogenous oscillations of Per1, Per2, Bmal1 and Rev-erbα genes in rat pineal explants and to investigate their regulation by adrenergic ligands. Our results show a significant and sustained rhythm of Per2,Bmal1 and Rev-erbα gene expression for up to 48 h in cultured pineal gland with a pattern similar to that observed in vivo. By contrast, the rhythms of Per1 and Aa-nat, the rate-limiting enzyme for melatonin synthesis, were strongly attenuated after 24 h in culture. Addition of the exogenous adrenergic agonist isoproterenol on cultured pineal glands induced a short-term increase in mRNA levels of Per1 and Aa-nat, but not those of Per2,Bmal1 and Rev-erbα. This study demonstrates that the rat pineal gland hosts a circadian oscillator as evidenced by the sustained, noradrenergic-independent, endogenous oscillations of Per2, Bmal1 and Rev-erbα mRNA levels in cultured tissues. Only expression of Per1 was stimulated by adrenergic ligands suggesting that, in vivo, the adrenergic input could synchronize the pineal clock by acting selectively on Per1.
authors.affiliation: Department of Anatomy, Srinakharinwirot University, Bangkok, Thailand.
authors.forename: Prapimpun
authors.initials: P
authors.lastname: Wongchitrat
authors.forename: Marie-Paule
authors.initials: MP
authors.lastname: Felder-Schmittbuhl
authors.forename: Piyarat
authors.initials: P
authors.lastname: Govitrapong
authors.forename: Pansiri
authors.initials: P
authors.lastname: Phansuwan-Pujito
authors.forename: Valérie
authors.initials: V
authors.lastname: Simonneaux
mesh_terms: D056930:ARNTL Transcription Factors / Q000378:metabolism*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001683:Biological Clocks / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D023421:Models, Animal; D056953:Nuclear Receptor Subfamily 1, Group D, Member 1 / Q000378:metabolism*; D009924:Organ Culture Techniques; D056950:Period Circadian Proteins / Q000378:metabolism*; D010656:Phenylephrine / Q000494:pharmacology; D010870:Pineal Gland / Q000378:metabolism*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D056930:ARNTL Transcription Factors; D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; 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; D010656:Phenylephrine; D011433:Propranolol; D007545:Isoproterenol