Transcription factors may frame Aa-nat gene expression and melatonin synthesis at night in the Syrian hamster pineal gland.
Pineal melatonin synthesis is stimulated at night following an increase in arylalkylamine-N-acetyltransferase (AA-NAT) activity. Depending on the species, two mechanisms of enzyme activation have been described: a cAMP/phospho-cAMP response element-binding protein-dependent stimulation of Aa-nat gene transcription in the rat, presumed to occur in all rodents, or a posttranslational regulation of AA-NAT protein in ongulates. The present data obtained in the Syrian hamster indicate another route of AA-NAT regulation. Elevated nocturnal levels of Aa-nat mRNA were strongly suppressed following light exposure or adrenergic antagonist administration, demonstrating the involvement of norepinephrine in the stimulation of melatonin synthesis. However, administration of adrenergic agonists during the day did not increase Aa-nat mRNA unless a protein synthesis inhibitor was given during the previous night. This indicates that an inhibitory protein, synthesized at night, prevents melatonin synthesis during the day. By contrast, a protein synthesis inhibitor given at the beginning of the night markedly reduced Aa-nat mRNA, suggesting that a stimulatory protein (transcription factor?) is necessary for Aa-nat gene transcription at night. Noteworthy, hamsters raised in long photoperiod were responsive to adrenergic agonist injection only in the first hour after light onset, a response that may be important in this photoperiodic species in which the melatonin peak extends into the morning hours in a short photoperiod.
Laboratoire de Neurobiologie des Rythmes, Unité Mixte Recherche-Centre National de la Recherche Scientifique-Université Louis Pasteur 7518, F-67000 Strasbourg, France.
Marie-Laure
ML
Garidou
Elena
E
Diaz
Christiane
C
Calgari
Paul
P
Pévet
Valérie
V
Simonneaux
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D002940:Circadian Rhythm / Q000502:physiology; D006224:Cricetinae; D003513:Cycloheximide / Q000494:pharmacology; D003624:Darkness; D005260:Female; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D007545:Isoproterenol / Q000494:pharmacology; D008029:Lighting; D008550:Melatonin / Q000096:biosynthesis* / Q000097:blood; D008647:Mesocricetus; D009638:Norepinephrine / Q000494:pharmacology; D017440:Photoperiod; D010870:Pineal Gland / Q000201:enzymology*; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D014157:Transcription Factors; D003513:Cycloheximide; D011433:Propranolol; D001191:Arylamine N-Acetyltransferase; D008550:Melatonin; D007545:Isoproterenol; D009638:Norepinephrine; D011224:Prazosin