CIRCADIAN REGULATION OF CREB TRANSCRIPTION FACTOR IN MOUSE ESOPHAGUS

Very little is known about the circadian regulation of cell entry into the S and M phases of the cell cycle. Yet, in the mouse esophagus, a seven-to ninefold increase in DNA synthesis coincides with nocturnal f eeding. The phosphorylation of the cAMP response element binding prote in (CREB), a transcriptional factor, may regulate hypothalamic circadi an rhythms in the brain. Here, we investigate the circadian regulation of CREB and Ser-133-phospho-CREB (PCREB) in the mouse esophagus by im munocytochemical and biochemical methods. We found that, during the da rk phase, coincident with the onset of feeding and increased DNA synth esis, esophageal CREB and PCREB expression decreased. Although CREB-li ke immunoreactivity (CREB-lir) was expressed in many different cell ty pes, it was concentrated in the mucosa, particularly in the replicatin g basal cell layer. The injection of epidermal growth factor, at a dos age known to maximally stimulate esophageal DNA synthesis in a 4- to 8 -h period, rapidly decreased PCREB levels within 10 min of injection. We speculate that PCREB-lir may be involved in the circadian regulatio n of cell cycle events in the intact mouse esophagus.