Comparative Aspects Of Signal Transduction Cascades Regulating Melatonin Biosynthesis

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As outlined above the transcriptional regulation of the AANAT plays an important role in up- and downregulation of melatonin synthesis in the rodent pineal organ. This scenario, however, does not apply for all vertebrates, not even for all mammals. In the sheep, posttranscriptional mechanisms are more relevant for control the rhythmic melatonin biosynthesis, as the mRNA for AANAT fluctuates only marginally (18). Accordingly, plasma melatonin concentrations rise after the onset of darkness much faster in sheep than in rodents (2).

Chicken, trout and most other non-mammalian vertebrate species possess photo-receptive pineal organs. Thus light rather than adrenergic-stimuli appear as primary regulators of the melatonin synthesis in these species. In the chicken pineal organ AANAT mRNA fluctuates, but with a much smaller amplitude than in the rat (36). Thus, chicken AANAT seems to be regulated at both, the transcriptional and the post-transcriptional levels. Accordingly, ICER has been reported to fluctuate diurnally in the chicken pineal organ (25). In the trout pineal organ where melatonin biosynthesis is regulated by light/dark stimuli directly perceived in the organ and is not affected by NE,AANAT mRNA does not fluctuate (10). Darkness, the natural stimulus of the trout pineal melatonin biosynthesis, has virtually no effect on CREB phosphorylation (Kroeber et al., unpublished results). Furthermore cAMP and pCREB showed virtually no variation over a 12 h light 12 h dark cycle, whereas melatonin displayed its characteristic rise in darkness which depends on calcium influx. The data show that in the trout pineal organ phosphorylation of CREB is not essential for the induction of the melatonin biosynthesis and imply that calcium is more essential for stimulation of mela-tonin biosynthesis than cAMP. These comparative considerations suggest that pCREB and ICER levels are tightly regulated and play an important role in those species in which the regulation of the melatonin biosynthesis bears a substantial transcriptional component.

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