Inducible cyclic AMP early repressor protein in rat pinealocytes: A highly sensitive natural reporter for regulated gene transcription

Martina Pfeffer, Erik Maronde, Carlos A. Molina, Horst Werner Korf, Jörg H. Stehle

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Rhythmic activity of arylalkylamine N-acetyltransferase (AANAT) determines melatonin synthesis in rat pineal gland. The transcriptional regulation of AANAT involves the activating and inhibiting transcription factors of the cyclic AMP (cAMP)-signaling pathway, cAMP response element- binding protein and inducible cAMP early repressor (ICER), respectively. Activation of this pathway is centered around norepinephrine, stimulating β1-adrenergic receptors, but various other transmitters can modulate melatonin biosynthesis. To compare the transcriptional impact of norepinephrine with that of other neurotransmitters on melatonin synthesis, we determined ICER protein levels in pinealocytes and, in parallel, hormone secretion. The dose-dependent inductions of-IC-ER protein by norepinephrine, the β1-adrenergic receptor agonist isoproterenol vasoactive intestinal peptide, pituitary adenylate cyclase-activating polypeptide, and adenosine are correlated to regulatory dynamics in melatonin production. Importantly ICER protein induction required lower ligand concentrations than the induction of melatonin biosynthesis. Although neuropeptide Y, glutamate, and vasopressin altered norepinephrine-stimulated hormone production without affecting ICER levels, the activation of voltage-gated cation channels increased ICIER without affecting hormone synthesis. Sensitivity and versatility of ICER induction in pinealocytes make these neuroendocrine cells a valuable model system in which to study molecular interactions determining a regulated gene expression.

Original languageEnglish
Pages (from-to)279-289
Number of pages11
JournalMolecular Pharmacology
Volume56
Issue number2
DOIs
StatePublished - 1 Jan 1999

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