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      Melatonin Translated title: Melatonina Translated title: Mélatonine

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          Abstract

          Melatonin (MEL) is a hormone synthesized and secreted by the pineal gland deep within the brain in response to photoperiodic cues relayed from the retina via an endogenous circadian oscillator within the suprachiasmatic nucleus in the hypothalamus. The circadian rhythm of melatonin production and release, characterized by nocturnal activity and daytime quiescence, is an important temporal signal to the body structures that can read it. Melatonin acts through high-affinity receptors located centrally and in numerous peripheral organs. Different receptor subtypes have been cloned and characterized: MT 1 and MT 2 (transmembrane G-protein-coupled receptors), and MT 3. However, their physiological role remains unelucidated, although livestock management applications already include the control of seasonal breeding and milk production. As for potential therapeutic applications, exogenous melatonin or a melatonin agonist and selective 5-hydroxytrypiamine receptor (5-HT 2c) antagonist, eg, S 20098, can be used to manipulate circadian processes such as the sleep-vake cycle, which are frequently disrupted in many conditions, most notably seasonal affective disorder.

          Translated abstract

          La melatonina (MEL) es una hormona que es sintetizada y secretada por la glándula pineal, la cual se ubica en la profundidad del cerebro, en respuesta a señales fotoperiódicas que se transmiten desde la retina a través de un oscilador circadiano que está en el núcleo supraquiasmático del hipo tálamo. El ritmo circadiano de la producción y liberación de melatonina, que se caracteriza por una actividad nocturna y un repose diurno, constituye una importante señal temporal para las estructuras del cuerpo que pueden leerla. La melatonina actúa a través de receptores de alta afinidad que se ubican a nivel central y en numerosos órganos periféricos. Se han clonado y caracterizado diferentes subtipos de receptores: MT 1 y MT 2 (receptores transmembranosos acoplados a proteína-G) y MT 3. Aun cuando su papel fisiológico no está aclarado, las aplicaciones en el manejo del ganado por ahora incluyen el control de la reproducción estacional y la producción de leche, Como potentiates aplicaciones terapéuticas la melatonina exógena o un agonista de melatonina y agonista selectivo del receptor 5-hidroxitryptamina (5-HT 2c), como el S 20098, se pueden utilizar para manipular los procesos circadianos como el ciclo sueño vigilia, el cual frecuentemente se desorganiza en muchas conditiones, en especial en el trastorno afectivo estacional.

          Translated abstract

          La melatonina (MEL) est une hormone synthétisée et sécrétée par l'épiphyse, glande située profondément dans le cerveau, en réponse à des signaux photopériodiques transmis à partir de la rétine par un oscillateur circadien endogène dans le noyau suprachiasmatique de l'hypothalamus. Le rythme circadien de la production et de la libération de mélatonine, caractérisé par une activité nocturne et une quiescence diurne, est un important signal temporel pour les structures corporelles capables de le lire. La mélatonine agit par l'intermédiaire de récepteurs à haute affinité, tant centraux que présents dans de nombreux organes périphétiques, Différents sous-types de récepteurs ont été clones et caractérisés: MT 1 et MT 2 (récepteurs transmembranaires couplés à la protéine G) et MT 3. Cependant, leur rôle physiologique reste non élucidé, bien que des applications de gestion du cheptel soient déjà utilisées pour contrôler la reproduction saisonnière et la production de lait. Dans les applications thérapeutiques potentielles, la mélatonine exogène ou par exemple, le S 20098, agoniste de la mélatonine et antagoniste sélectif du récepteur de la 5-hydroxytrypiamine (5-HT 2c), peuvent être utilisés pour modifier certains processus circadiens comme le cycle veille-sommeil, qui sont souvent déréglés dans de nombreuses circonstances, tout particulièrement dans les troubles affectifs saisonniers.

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          Most cited references 175

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          Interacting molecular loops in the mammalian circadian clock.

          We show that, in the mouse, the core mechanism for the master circadian clock consists of interacting positive and negative transcription and translation feedback loops. Analysis of Clock/Clock mutant mice, homozygous Period2(Brdm1) mutants, and Cryptochrome-deficient mice reveals substantially altered Bmal1 rhythms, consistent with a dominant role of PERIOD2 in the positive regulation of the Bmal1 loop. In vitro analysis of CRYPTOCHROME inhibition of CLOCK: BMAL1-mediated transcription shows that the inhibition is through direct protein:protein interactions, independent of the PERIOD and TIMELESS proteins. PERIOD2 is a positive regulator of the Bmal1 loop, and CRYPTOCHROMES are the negative regulators of the Period and Cryptochrome cycles.
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            Molecular analysis of mammalian circadian rhythms.

            In mammals, a master circadian "clock" resides in the suprachiasmatic nuclei (SCN) of the anterior hypothalamus. The SCN clock is composed of multiple, single-cell circadian oscillators, which, when synchronized, generate coordinated circadian outputs that regulate overt rhythms. Eight clock genes have been cloned that are involved in interacting transcriptional-/translational-feedback loops that compose the molecular clockwork. The daily light-dark cycle ultimately impinges on the control of two clock genes that reset the core clock mechanism in the SCN. Clock-controlled genes are also generated by the central clock mechanism, but their protein products transduce downstream effects. Peripheral oscillators are controlled by the SCN and provide local control of overt rhythm expression. Greater understanding of the cellular and molecular mechanisms of the SCN clockwork provides opportunities for pharmacological manipulation of circadian timing.
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              Molecular characterization of a second melatonin receptor expressed in human retina and brain: the Mel1b melatonin receptor.

              A G protein-coupled receptor for the pineal hormone melatonin was recently cloned from mammals and designated the Mel1a melatonin receptor. We now report the cloning of a second G protein-coupled melatonin receptor from humans and designate it the Mel1b melatonin receptor. The Mel1b receptor cDNA encodes a protein of 362 amino acids that is 60% identical at the amino acid level to the human Mel1a receptor. Transient expression of the Mel1b receptor in COS-1 cells results in high-affinity 2-[125I]iodomelatonin binding (Kd = 160 +/- 30 pM). In addition, the rank order of inhibition of specific 2-[125I]iodomelatonin binding by eight ligands is similar to that exhibited by the Mel1a melatonin receptor. Functional studies of NIH 3T3 cells stably expressing the Mel1b melatonin receptor indicate that it is coupled to inhibition of adenylyl cyclase. Comparative reverse transcription PCR shows that the Mel1b melatonin receptor is expressed in retina and, to a lesser extent, brain. PCR analysis of human-rodent somatic cell hybrids maps the Mel1b receptor gene (MTNR1B) to human chromosome 11q21-22. The Mel1b melatonin receptor may mediate the reported actions of melatonin in retina and participate in some of the neurobiological effects of melatonin in mammals.
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                Author and article information

                Contributors
                Laboratoire de Neurobiologie des Rythmes, UMR 7518 CNRS-Université Louis Pasteur, Strasbourg, France
                Journal
                Dialogues Clin Neurosci
                Dialogues Clin Neurosci
                Dialogues in Clinical Neuroscience
                Les Laboratoires Servier (France )
                1294-8322
                1958-5969
                March 2002
                March 2002
                : 4
                : 1
                : 57-72
                Affiliations
                Laboratoire de Neurobiologie des Rythmes, UMR 7518 CNRS-Université Louis Pasteur, Strasbourg, France
                Author notes
                Article
                3181670
                22034091
                Copyright: © 2002 LLS

                This is an open-access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Pharmacological Aspects

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