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

Neurotransmitter-driven activation of transcription factors is important fo r control of neuronal and neuroendocrine functions. We show with an in vivo approach that the norepinephrine cAMP-dependent rhythmic hormone productio n in rat pineal gland is accompanied by a temporally regulated switch in th e ratio of a transcriptional activator, phosphorylated cAMP-responsive elem ent-binding protein (pCREB), and a transcriptional inhibitor, inducible cAM P early repressor (ICER). pCREB accumulates endogenously at the beginning o f the dark period and declines during the second half of the night. Concomi tant with this decline, the amount of ICER rises. The changing ratio betwee n pCREB and ICER shapes the in vivo dynamics in mRNA and, thus, protein lev els of arylalkylamine-N-acetyltransferase, the rate-limiting enzyme of mela tonin synthesis. Consequently, a silenced ICER expression in pinealocytes l eads to a disinhibited arylalkylamine-N-acetyltransferase transcription and a primarily enhanced melatonin synthesis.