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-acetyltransferase [arylalkylamine N-acetyltransferase (AA-NAT); EC 2.3.1.87] drives the daily rhythm in circulating melatonin. We have discovered that expression of the AA-NAT gene in the rat pineal gland is essentially 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 phosphorylation. Turning off AA-NAT expression appears to involve de novo synthesis of a protein that attenuates transcription. A approximately 10-fold night/day rhythm in AA-NAT messenger RNA occurs in the retina, and AA-NAT messenger RNA is also detected at low levels in the brain.
Roseboom
P H
PH
Section on Neuroendocrinology, Laboratory of Developmental Neurobiology, National Institute of Child Health and Human Development, National Institute of Health, Bethesda, Maryland 20892-4480.
Coon
S L
SL
Baler
R
R
McCune
S K
SK
Weller
J L
JL
Klein
D C
DC
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000096:biosynthesis* / Q000737:chemistry; D001921:Brain / Q000201:enzymology*; D002940:Circadian Rhythm; D016384:Consensus Sequence; D018076:DNA, Complementary; D003624:Darkness; D008027:Light; D008297:Male; D008550:Melatonin / Q000096:biosynthesis*; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010656:Phenylephrine / Q000494:pharmacology; D010870:Pineal Gland / Q000201:enzymology* / Q000502:physiology; D016133:Polymerase Chain Reaction; D011433:Propranolol / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D017386:Sequence Homology, Amino Acid; D012756:Sheep; D014158:Transcription, Genetic
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D018076:DNA, Complementary; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D010656:Phenylephrine; D011433:Propranolol; D001191:Arylamine N-Acetyltransferase; D008550:Melatonin