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The Journal of Neuroscience, May 1, 1999, 19(9):3326-3336
Transcription Factors in Neuroendocrine Regulation: Rhythmic Changes in pCREB and ICER Levels Frame Melatonin Synthesis
Erik Maronde1, Martina Pfeffer1, James Olcese2, Carlos A. Molina3, Florence Schlotter3, Faramarz Dehghani1, Horst-Werner Korf1, and Jörg H. Stehle1 1 Dr. Senckenbergische Anatomie, Institute for Anatomy II, Johann Wolfgang Goethe-University Frankfurt, 60590 Frankfurt, Germany, 2 Institute for Hormone and Fertility Research, University of Hamburg, 22529 Hamburg, Germany, and 3 Department of Obstetrics and Gynecology, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103-2714
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.
Key words: pineal gland; CREB (cAMP-responsive element-binding protein); melatonin; arylalkylamine-N-acetyltransferase; transcription factor; ICER (inducible cAMP early repressor); circadian rhythm; antisense; cAMP signaling
Copyright © 1999 Society for Neuroscience 0270-6474/99/1993326-11$05.00/0
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