REVIEW Circadian Signaling in the Chick Pineal Organ James Olcese * Institute for Hormone and Fertility Research, University of Hamburg, Hamburg, Germany ABSTRACT The chick pineal organ is recognized to contain an endogenous circadian oscillator as well as having direct photic input pathways and the capability of synthesizing melatonin. Despite its interesting circadian cell biology, far less is known about the chick pineal as compared to mammalian pineal glands. The goals of our research were to identify and characterize novel components of the circadian system in this photo- neuroendocrine organ. Using a subtractive screening strategy of a nocturnal chick pineal cDNA library, we identified numerous genes whose expression in the chick pineal has never been reported. Among these, we focused our attention on a homologue to the regulatory subunit of the mammalian serine=threonine protein phosphatase (STPP) 2A. The expression of this gene in the chick pineal is highly circadian both in vivo and in vitro. Analysis of the PP2A enzyme in this tissue revealed that it is predominantly cytosolic in localization, sensitive to classical PP2A inhibitors, and far more active during the subjective night. Interestingly, the acute pharmacological inhibition of PP2A leads to elevated phosphoCREB levels and concomitant melatonin secretion, indicating that this enzyme participates at some level in the control of nocturnal pineal melatonin synthesis. In a second aspect of our research, we examined the mechanisms underlying the circadian rhythmicity of cyclic GMP in the chick pineal. This signaling molecule is poorly understood, despite its well-known, high- amplitude circadian rhythms and the presence of many cGMP-dependent targets in this tissue. Our work has shown that although both soluble (sGC) and membrane-bound * Correspondence: James Olcese, Institute for Hormone and Fertility Research, University of Hamburg, Grandweg 64, 22529 Hamburg, Germany; E-mail: olcese@ihf.de. CHRONOBIOLOGY INTERNATIONAL Vol. 20, No. 4, pp. 617–636, 2003 DOI: 10.1081=CBI-120022409 0742-0528 (Print); 1525-6073 (Online) Copyright # 2003 by Marcel Dekker, Inc. www.dekker.com 617