Differential adrenergic regulation of the circadian expression of the clock genes Period1 and Period2 in the rat pineal gland

Precise temporal regulation of transcription is pivotal to the role of the mammalian pineal gland as a transducer of circadian and seasonal informatio n. The circadian clock genes Per1 and Per2 encode factors implicated in tem porally gated transcriptional programmes in brain and pituitary. Here we sh ow that the nocturnal circadian expression of Per1 and Per2 in the rat pine al gland parallels that of serotonin N-acetyltransferase (NAT) mRNA, which encodes the rate-limiting enzyme of melatonin biosynthesis. This rhythm is dependent upon an intact sympathetic innervation. Increases in rPer1 (r ind icates rat) and rPer2 as well as rNAT, expression during subjective night w ere blocked completely by superior cervical ganglionectomy (SCGX). In SCGX rats, the beta -adrenergic receptor agonist isoproterenol rapidly induced t he rPer1 mRNA with dynamics very similar to its effect on rNAT mRNA. In con trast, isoproterenol was without effect on expression of rPer2 mRNA. These findings demonstrate that circadian pineal expression of both rPer1 and rPe r2 is controlled by sympathetic afferent innervation, but whereas P-adrener gic signalling regulates rPer1 and rNAT, an alternative route mediates symp athetic regulation over rPer2 expression.