MELATONIN SYNTHESIS - ANALYSIS OF THE MORE THAN 150-FOLD NOCTURNAL INCREASE IN SEROTONIN N-ACETYLTRANSFERASE MESSENGER-RIBONUCLEIC-ACID IN THE RAT PINEAL-GLAND

In vertebrates, the circadian rhythm in the activity of serotonin N-ac etyltransferase [arylalkylamine N-acetyltransferase (AA-NAT); EC 2.3.1 .87] drives the daily rhythm in circulating melatonin. We have discove red that expression of the AA-NAT gene in the rat pineal gland is esse ntially turned off during the day and turned on at night, resulting in a more than 150-fold rhythm. Expression is regulated by a photoneural system that acts through an adrenergic-cAMP mechanism in pinealocytes , probably involving cAMP response element-binding protein phosphoryla tion. Turning off AA-NAT expression appears to involve de novo synthes is of a protein that attenuates transcription. A similar to 10-fold ni ght/day rhythm in AA-NAT messenger RNA occurs in the retina, and AA-NA T messenger RNA is also detected at low levels in the brain.