This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ribelayga, C. Articles by Simonneaux, V. Search for Related Content PubMed PubMed Citation Articles by Ribelayga, C. Articles by Simonneaux, V.

Photoneural Regulation of Rat Pineal Hydroxyindole-O-Methyltransferase (HIOMT) Messenger Ribonucleic Acid Expression: An Analysis of Its Complex Relationship with HIOMT Activity¹

Neurobiologie des Fonctions Rythmiques et Saisonnières, Unité Mixte de Recherche-Centre National de la Recherche Scientifique 7518, Université Louis Pasteur, F-67000 Strasbourg, France

Address all correspondence and requests for reprints to: Dr. Valérie Simonneaux, Neurobiologie des Fonctions Rythmiques et Saisonnières, Unité Mixte de Recherche-Centre National de la Recherche Scientifique 7518, Université Louis Pasteur, 12 rue de l’Université, F-67000 Strasbourg, France. E-mail: simonneaux{at}neurochem.u-strasbg.fr

In the pineal gland, synthesis of melatonin requires O-methylation catalyzed by hydroxyindole-O-methyltransferase (HIOMT; EC 2.1.1.4). We investigated in vivo the molecular mechanisms involved in the regulation of rat pineal HIOMT messenger RNA (mRNA) expression and activity using in situ hybridization and radioenzymatic assay. HIOMT mRNA levels and activity are both detectable during the daytime and display nocturnal increases of 100% and 30%, respectively. These variations are controlled by the endogenous clock, as they persist in constant darkness. The nocturnal increase in HIOMT mRNA mainly results from a ß₁-adrenergic stimulation of HIOMT gene expression without requiring de novo synthesis of a transcription factor. In contrast, the nocturnal increase in HIOMT activity appears independent of ß₁/₁-adrenergic stimulation. A light pulse at night abolishes the nighttime increase in HIOMT mRNA, but not HIOMT activity. Constant light application for up to 11 days does not depress HIOMT mRNA levels lower than the daytime levels, but decreases enzyme activity down to 50% of the daytime level. This finding indicates that the nocturnal stimulation of HIOMT gene expression is required for sustaining a basal level of activity over a few days. Our data suggest 1) that HIOMT gene expression is partly regulated by ß₁-stimulation; and 2) that HIOMT activity is regulated over the short term by a nonnoradrenergic stimulus and over the long term by noradrenergic stimulation.

This article has been cited by other articles:

				J. R. Man, S. Rustaeus, D. M. Price, C. L. Chik, and A. K. Ho Inhibition of p38 Mitogen-Activated Protein Kinase Enhances Adrenergic-Stimulated Arylalkylamine N-Acetyltransferase Activity in Rat Pinealocytes Endocrinology, March 1, 2004; 145(3): 1167 - 1174. [Abstract] [Full Text] [PDF]

				V. Simonneaux and C. Ribelayga Generation of the Melatonin Endocrine Message in Mammals: A Review of the Complex Regulation of Melatonin Synthesis by Norepinephrine, Peptides, and Other Pineal Transmitters Pharmacol. Rev., June 1, 2003; 55(2): 325 - 395. [Abstract] [Full Text] [PDF]

				M.-L. Garidou, B. Vivien-Roels, P. Pevet, J. Miguez, and V. Simonneaux Mechanisms regulating the marked seasonal variation in melatonin synthesis in the European hamster pineal gland Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2003; 284(4): R1043 - R1052. [Abstract] [Full Text] [PDF]

				C. Ribelayga, P. Pevet, and V. Simonneaux HIOMT drives the photoperiodic changes in the amplitude of the melatonin peak of the Siberian hamster Am J Physiol Regulatory Integrative Comp Physiol, May 1, 2000; 278(5): R1339 - R1345. [Abstract] [Full Text] [PDF]