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Several investigations have shown that illumination at night reduces melatonin level in the mammalian pineal, but the effect of night illumination on the retina is not known. In this study retinas were cultured in a flow-through apparatus and then were exposed to light at ZT 18. Light exposure reduced melatonin levels to the daytime level within 30 min. The reduction of melatonin levels was due to a rapid decrease in the activity of the enzyme AA-NAT; AA-NAT mRNA levels were not affected by illumination. Pre-incubation with lactacystin (25 microM) prevented light-induced reduction of AA-NAT activity and melatonin levels. These results demonstrate that melatonin levels in the mammalian retina are affected by light exposure at night, via proteosomal proteolysis of AA-NAT.

The aim of the present study was to investigate the in vitro expression of Period 1 (Per1), Period 2 (Per2) and arylalkylamine N-acetyltransferase (AA-NAT) genes in the rat pineal gland to understand the mechanism(s) regulating the expression of these genes in this organ. Pineals, when maintained in vitro for 5 days, did not show circadian rhythmicity in the expression of any of the three genes monitored. Norepinephrine (NE) induced AA-NAT and Per1, whereas its effect on Per2 was negligible. Contrary to what was observed in other systems, NE stimulation did not induce circadian expression of Per1. The effect of NE on Per1 level was dose- and receptor subtype-dependent, and both cAMP and cGMP induced Per1. Per1 was not induced by repeated NE – or forskolin – stimulation. Protein synthesis was not necessary for NE-induced Per1, but it was for reduction of Per1 following NE stimulation. Per1 transcription in pinealocytes was activated by BMAL1/CLOCK. Our results indicate that important differences are present in the regulation of these genes in the mammalian pineal.

Several studies have demonstrated that norepinephrine (NE) is the critical neurotransmitter for the regulation of gene expression in the pineal gland. We studied the acute effect of NE stimulation in cultured rat pineal glands using Affymetrix rat genome microarray GeneChip probe arrays. Our data demonstrate that NE stimulation affects regulation of several genes; 44 and 29 genes were up‐ or down‐regulated more than 2.5‐fold, respectively. As shown in previous studies, arylalkylamine N‐acetyltransferase, cyclic AMP responsive element modulator, jun‐B and c‐fos mRNA levels were increased by NE stimulation. Genes that were not previously reported and increased by NE stimulation in the pineal gland were protein tyrosine phosphatase, nuclear receptors, and activity and neurotransmitter‐induced early genes. Unlike up‐regulated genes, most of the down‐regulated genes were not reported previously. Genes encoding enzymes involved in metabolism and structural proteins were decreased following NE stimulation. Identification of genes affected by NE stimulation would provide valuable information to understanding pineal biology fully.