Hydroxyindole-O-methyltransferase, a Season-coding Enzyme for Melatonin Synthesis in the Pineal Gland of Rodents

Abstract

The time giver hormone melatonin is secreted with both daily and seasonal rhythms in the mammalian pineal gland. We report here that the two main melatoninsynthesizing enzymes N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT) are differently involved in the regulation of the daily and photoperiodic rhythms of melatonin synthesis. The activity of the unstable NAT enzyme is stimulated acutely at night by norepinephrine via cAMP-dependent transcriptional mechanisms, indicating that it triggers the nocturnal increase in melatonin synthesis and drives its duration according to the night length. In contrast, the activity of the stable HIOMT enzyme is regulated chronically by a norepinephrine-induced, 2-fold increase in HIOMT mRNA that occurs every night. Such regulation leads to a photoperiodic variation in HIOMT activity which is positively related to duration of the night. Whether in vivo or in vitro, at high NAT activity, HIOMT activity appears to limit the amount of melatonin release. This suggests that HIOMT activity may tune the amplitude of the nocturnal increase in pineal melatonin secretion with photoperiodic variations.