ABSTRACT
Melatonin is mainly secreted by the pineal gland into the blood circulation in most species studied. It was demonstrated by Weissbach et al. that N-acetylation of serotonin to N-acetylserotonin (NAS) is involved in melatonin biosynthesis. The final conversion of NAS to melatonin was also found to be an enzymatic process; an enzyme called hydroxyindole-O-methyltransferase responsible for the O-methylation step of NAS was purified and characterized by Axelrod and Weissbach in 1961. They found that this enzyme was highly localized in the pineal gland, so melatonin biosynthesis was thought to be carried out solely in this organ. Since the notion of melatonin biosynthesis in extrapineal tissues is relatively new, an understanding of melatonin biosynthesis is based primarily on studies on the pineal. An alternative regulatory mechanism of melatonin biosynthesis directly dependent on the light-dark cycle may exist in some mammals. Limited information is available on the regulation of melatonin biosynthesis in the mammalian retina.
