Night/day changes in pineal expression of >600 genes: central role of adrenergic/cAMP signaling

J Biol Chem. 2009 Mar 20;284(12):7606-22. doi: 10.1074/jbc.M808394200. Epub 2008 Dec 22.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Circadian Rhythm / physiology*
  • Cyclic AMP / metabolism
  • Gene Expression Profiling / methods
  • Gene Expression Regulation / physiology*
  • Norepinephrine / metabolism
  • Oligonucleotide Array Sequence Analysis / methods
  • Organ Specificity
  • Pineal Gland / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Retina / metabolism

Substances

  • Cyclic AMP
  • Norepinephrine