Melatonin biosynthesis in chicken retina: regulation of tryptophan hydroxylase and arylalkylamine N-acetyltransferase
Résumé
Melatonin is synthesized from the amino acid tryptophan (tryptophan -> 5-hydroxytryptophan -> serotonin -> N-acetylserotonin -> melatonin). In the chick retina, mRNA levels and activities of two enzymes in this pathway, tryptophan hydroxylase (TPH) and arylalkylamine N-acetyltranferase (AA - NAT), display circadian rhythms. The dramatic nocturnal increase in melatonin production in this tissue in part reflects circadian clock-driven increases in mRNA encoding both enzymes. This appears to be translated into increases in both TPH and AA-NAT protein. In the case of AA-NAT, however, this translation is strongly dependent upon environmental lighting. Light acts through post-transcriptional mechanisms to regulate AA-NAT activity: a hypothetical mechanism is proteasomal proteolysis that is otherwise inhibited in the dark by second messengers. Accordingly, melatonin production in the retina, as in the chicken pineal gland, is thought to be regulated by two mechanisms. One is clock- driven changes in TPH and AA-NAT mRNAs, which in turn drive changes in the synthesis of the corresponding encoded proteins. The second is light-induced post-transcriptional degradation of AA-NAT. These mechanisms insure that retinal melatonin production follows a precise schedule that reflects daily changes in the envi - ronmental lighting.