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Twenty-Four-Hour Rhythmic Gene Expression in the Rhesus Macaque Adrenal Gland

Division of Neuroscience, Oregon National Primate Research Center, Beaverton, Oregon 97006

Address all correspondence and requests for reprints to: Henryk F. Urbanski, Division of Neuroscience, Oregon National Primate Research Center, 505 Northwest 185th Avenue, Beaverton, Oregon 97006. E-mail: urbanski{at}ohsu.edu.

The suprachiasmatic nucleus plays a key role in the circadian secretion of adrenocortical hormones. However, there is evidence from mouse studies that components of the circadian clock are also expressed within the adrenal gland itself. In the present study we performed genome-wide expression profiling to determine whether the adrenal gland of rhesus monkeys shows temporal gene expression across a 24-h period. We identified 322 transcripts with rhythmic patterns of expression and found that the phase distribution of cycling transcripts varied across the day, with more genes showing activation during the night. We classified the transcripts by their function and clustered them according to their participation in common biochemical pathways: 1) catecholamine synthesis and reuptake; 2) cholesterol cleavage and dehydroepiandrosterone sulfate synthesis; 3) protein synthesis and turnover; and 4) the circadian clock mechanism. In an additional experiment, we assessed the expression of various clock genes at two time points, 12 h apart. We found that expression of Bmal1 and Cry1 was higher at 1300 h, or zeitgeber time 6, whereas expression of Per1 was higher at 0100 h (zeitgeber time 18). Expression levels of Rev-erb were higher at 0100 h than at 1300 h (P < 0.05), and immunohistochemistry revealed a strong expression of this transcription factor specifically in chromaffin cells of the adrenal medulla. Taken together, the data indicate that the primate adrenal gland shows rhythmic expression of genes associated with cell biology and synthesis of steroids and catecholamines. Moreover, they strongly imply the existence of an intrinsic circadian clock.

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