Intestinal production of melatonin and its putative role as a circadian organizer

Pineal melatonin is a potent synchronizer within the circadian system. Certain extra-pineal tissues also synthesize melatonin, including the gastrointestinal organs, whose melatonin contents can exceed that of pineal severalfold. Considering the role of pineal melatonin as a general synchronizer, we investigated whether the intestinal melatonin could serve a similar role in the local organization of the metabolic events, as a core element of the Food-Entrainable Oscillator (FEO). To be considered so, the intestinal secretory activity should meet some requirements: it should have self-sustained rhythmicity, that should also be synchronized to but not depend on feeding. To test this, we analyzed the circadian expression of the rate-limiting enzyme of melatonin synthesis, AANAT, in the intestine of rats. We found that AANAT expression varies along the intestine and shows a clear circadian pattern only in the proximal (duodenal) and distal (colonic) edges. The circadian variation in duodenum was abolished by fasting, implying that this activity is not self-sustained but reactive to feeding. The colon had the highest AANAT expression that was also rhythmic, but the phase of this rhythm was not synchronized to feeding. We propose that intestinal melatonin derives from different populations of secreting cells, but none of these populations meets the criteria for a pacemaker underlying the FEO.