Transcription factors in neuroendocrine regulation: rhythmic changes in pCREB and ICER levels frame melatonin synthesis.
Neurotransmitter-driven activation of transcription factors is important for control of neuronal and neuroendocrine functions. We show with an in vivo approach that the norepinephrine cAMP-dependent rhythmic hormone production in rat pineal gland is accompanied by a temporally regulated switch in the ratio of a transcriptional activator, phosphorylated cAMP-responsive element-binding protein (pCREB), and a transcriptional inhibitor, inducible cAMP early repressor (ICER). pCREB accumulates endogenously at the beginning of the dark period and declines during the second half of the night. Concomitant with this decline, the amount of ICER rises. The changing ratio between pCREB and ICER shapes the in vivo dynamics in mRNA and, thus, protein levels of arylalkylamine-N-acetyltransferase, the rate-limiting enzyme of melatonin synthesis. Consequently, a silenced ICER expression in pinealocytes leads to a disinhibited arylalkylamine-N-acetyltransferase transcription and a primarily enhanced melatonin synthesis.
Maronde
E
E
Dr. Senckenbergische Anatomie, Institute for Anatomy II, Johann Wolfgang Goethe-University Frankfurt, 60590 Frankfurt, Germany.
Pfeffer
M
M
Olcese
J
J
Molina
C A
CA
Schlotter
F
F
Dehghani
F
F
Korf
H W
HW
Stehle
J H
JH
D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D002940:Circadian Rhythm; D000242:Cyclic AMP / Q000378:metabolism; D051786:Cyclic AMP Response Element Modulator; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D008550:Melatonin / Q000096:biosynthesis*; D009638:Norepinephrine / Q000494:pharmacology; D009924:Organ Culture Techniques; D010766:Phosphorylation; D010870:Pineal Gland / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000096:biosynthesis; D012097:Repressor Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D014162:Transfection
D017362:Cyclic AMP Response Element-Binding Protein; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012097:Repressor Proteins; D051786:Cyclic AMP Response Element Modulator; D000242:Cyclic AMP; D001191:Arylamine N-Acetyltransferase; D008550:Melatonin; D009638:Norepinephrine