title: Night/day changes in pineal expression of >600 genes: central role of adrenergic/cAMP signaling.
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(R) 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 approximately 70%. 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.
authors.affiliation: Section on Neuroendocrinology, Program on Developmental Endocrinology and Genetics, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bailey
authors.forename: Steven L
authors.initials: SL
authors.lastname: Coon
authors.forename: David A
authors.initials: DA
authors.lastname: Carter
authors.forename: Ann
authors.initials: A
authors.lastname: Humphries
authors.forename: Jong-So
authors.initials: JS
authors.lastname: Kim
authors.forename: Qiong
authors.initials: Q
authors.lastname: Shi
authors.forename: Pascaline
authors.initials: P
authors.lastname: Gaildrat
authors.forename: Fabrice
authors.initials: F
authors.lastname: Morin
authors.forename: Surajit
authors.initials: S
authors.lastname: Ganguly
authors.forename: John B
authors.initials: JB
authors.lastname: Hogenesch
authors.forename: Joan L
authors.initials: JL
authors.lastname: Weller
authors.forename: Martin F
authors.initials: MF
authors.lastname: Rath
authors.forename: Morten
authors.initials: M
authors.lastname: Møller
authors.forename: Ruben
authors.initials: R
authors.lastname: Baler
authors.forename: David
authors.initials: D
authors.lastname: Sugden
authors.forename: Zoila G
authors.initials: ZG
authors.lastname: Rangel
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Munson
authors.forename: David C
authors.initials: DC
authors.lastname: Klein
mesh_terms: D000818:Animals; D002940:Circadian Rhythm / Q000502:physiology*; D000242:Cyclic AMP / Q000378:metabolism; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D009928:Organ Specificity; D010870:Pineal Gland / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000378:metabolism
chemical_list: D000242:Cyclic AMP; D009638:Norepinephrine