Transcription factors in neuroendocrine regulation: Rhythmic changes in pCREB and ICER levels frame melatonin synthesis

Erik Maronde, Martina Pfeffer, James Olcese, Carlos A. Molina, Florence Schlotter, Faramarz Dehghani, Horst Werner Korf, Jörg H. Stehle

Research output: Contribution to journalArticle

110 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)3326-3336
Number of pages11
JournalJournal of Neuroscience
Volume19
Issue number9
StatePublished - 1 May 1999

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Keywords

  • Antisense
  • Arylalkylamine-N-acetyltransferase
  • CAMP signaling
  • CREB (cAMP-responsive element-binding protein)
  • Circadian rhythm
  • ICER (inducible cAMP early repressor)
  • Melatonin
  • Pineal gland
  • Transcription factor

Cite this

Maronde, E., Pfeffer, M., Olcese, J., Molina, C. A., Schlotter, F., Dehghani, F., Korf, H. W., & Stehle, J. H. (1999). Transcription factors in neuroendocrine regulation: Rhythmic changes in pCREB and ICER levels frame melatonin synthesis. Journal of Neuroscience, 19(9), 3326-3336.