Signal Transduction Molecules in the Rat Pineal Organ: Ca2+, pCREB, and ICER

Abstract

The mammalian pineal organ transduces light-dependent neural inputs into a hormonal output. This photoneuroendocrine transduction results in a largely elevated concentration of the pineal hormone melatonin at night. The rhythm in melatonin production and secretion depends on activation and inactivation of transcriptional, translational, and posttranslational mechanisms fundamentally linked to two second messenger systems, the cAMP- and the Ca(2+)-signal transduction pathways. Here we review molecular biological, immunocytochemical, and single-cell imaging studies, which demonstrate a time- and substance-specific activation of these signaling pathways in rat pinealocytes. The data provide a framework for understanding the complex interactions between second messengers (cAMP, Ca2+), transcription factors (CREB, ICER), and their role in regulation of melatonin synthesis. The data have proven the rat pinealocyte to be an interesting model to study transmembrane signaling pathways which may be common to both neuroendocrine and neuronal cells.

Regulation of Inducible cAMP Early Repressor Expression by Gastrin and Cholecystokinin in the Pancreatic Cell Line AR42J

“…CREM appears to play a decisive role in the regulation of the spermatogenetic process (7), and studies with CREM gene knock-out mice display animals that completely lack spermatozoa and are sterile (19). In particular, inducibility of the ICER repressor has been reported to occur in several tissues in response to hormone stimulation, first described in the hypothalamic-pituitary-gonadal axis and in the pineal gland (1,17,20,21).…”

A Semiquantitative Image-analytical Method for the Recording of Dose-Response Curves in Immunocytochemical Preparations

“…The method was developed using a well-characterized cell culture system, i.e., isolated rat pinealocytes (Tamotsu et al 1995;Korf et al 1996;Maronde et al 1997b). In these cells, adrenergic stimulation induces melatonin biosynthesis by activating the cAMP pathway (see Klein et al 1996).…”

Regulation of Period 1 Expression in Cultured Rat Pineal

“…The SCN sends day-night information to the pineal gland through sympathetic innervation and by the release of norepinephrine (NE) from the nerve endings [7]. NE activates adrenergic receptors to increase cyclic AMP (cAMP) and intracellular calcium with the consequent phosphorylation of the cAMP response element (CRE) binding pro-Fukuhara/Dirden/Tosini teins (CREB) [8,9]. Such events lead to the transcriptional activation of the arylalkylamine N-acetyltransferase (AA-NAT) gene, the key enzyme in the melatonin biosynthetic pathway, and thus to the activation of melatonin synthesis [10].…”