No abstract

The pineal gland plays an essential role in vertebrate chronobiology by converting time into a hormonal signal, melatonin, which is always elevated at night. Here we have analyzed the rodent pineal transcriptome using Affymetrix GeneChip technology to obtain a more complete description of pineal cell biology. The effort revealed that 604 genes (1,268 probe sets) with Entrez Gene identifiers are differentially expressed greater than 2-fold between midnight and mid-day (false discovery rate <0.20). Expression is greater at night in ϳ70%. These findings were supported by the results of radiochemical in situ hybridization histology and quantitative real time-PCR studies. We also found that the regulatory mechanism controlling the night/ day changes in the expression of most genes involves norepinephrine-cyclic AMP signaling. Comparison of the pineal gene expression profile with that in other tissues identified 334 genes (496 probe sets) that are expressed greater than 8-fold higher in the pineal gland relative to other tissues. Of these genes, 17% are expressed at similar levels in the retina, consistent with a common evolutionary origin of these tissues. Functional categorization of the highly expressed and/or night/day differentially expressed genes identified clusters that are markers of specialized functions, including the immune/inflammation response, melatonin synthesis, photodetection, thyroid hormone signaling, and diverse aspects of cellular signaling and cell biology. These studies produce a paradigm shift in our understanding of the 24-h dynamics of the pineal gland from one focused on melatonin synthesis to one including many cellular processes.A defining feature of the pineal gland is a 24-h rhythm in melatonin synthesis. Melatonin provides vertebrates with a circulating signal of time and is essential for optimal integration of physiological functions with environmental lighting on a daily and seasonal basis (1-4).The melatonin rhythm in mammals is driven by a circadian clock located in the suprachiasmatic nucleus (SCN), 13 which is hard-wired to the pineal gland by a polysynaptic pathway that courses through central and peripheral neuronal structures. The pineal gland is innervated by projections from the superior cervical ganglia (SCG) in the form of a dense network of catecholamine-containing sympathetic fibers. Activation of the SCN 3 pineal pathway occurs at night and results in the release