A Noradrenergic Sensitive Endogenous Clock Is Present in the Rat Pineal Gland

作者：Wongchitrat Prapimpun; Felder Schmittbuhl Marie Paule; Govitrapong Piyarat; Phansuwan Pujito Pansiri; Simonneaux Valerie^*

来源：Neuroendocrinology, 2011, 94(1): 75-83.

DOI：10.1159/000327430

• Circadian oscillator
• Rev-erb alpha
• Bmal1
• Clock gene
• Pineal gland

The aim of this study was to examine the occurrence of endogenous oscillations of Per1, Per2, Bmal1 and Rev-erb alpha 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-erb alpha 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-erb alpha. 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-erb alpha 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.

• 出版日期2011