Night/day changes in pineal expression of >600 genes: central role of adrenergic/cAMP signaling.
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.
Bailey
Michael J
MJ
Section on Neuroendocrinology, Program on Developmental Endocrinology and Genetics, NICHD, National Institutes of Health, Bethesda, Maryland 20892, USA.
Coon
Steven L
SL
Carter
David A
DA
Humphries
Ann
A
Kim
Jong-So
JS
Shi
Qiong
Q
Gaildrat
Pascaline
P
Morin
Fabrice
F
Ganguly
Surajit
S
Hogenesch
John B
JB
Weller
Joan L
JL
Rath
Martin F
MF
Møller
Morten
M
Baler
Ruben
R
Sugden
David
D
Rangel
Zoila G
ZG
Munson
Peter J
PJ
Klein
David C
DC
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
D000242:Cyclic AMP; D009638:Norepinephrine