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Review ArticleReview

Generation of the Melatonin Endocrine Message in Mammals: A Review of the Complex Regulation of Melatonin Synthesis by Norepinephrine, Peptides, and Other Pineal Transmitters

Valerie Simonneaux and Christophe Ribelayga
Pharmacological Reviews June 2003, 55 (2) 325-395; DOI: https://doi.org/10.1124/pr.55.2.2
Valerie Simonneaux
Laboratoire de Neurobiologie des Rythmes, Unité Mixte Recherche 7518, Centre National de la Recherche Scientifique/Université Louis Pasteur, Strasbourg, France
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Christophe Ribelayga
Laboratoire de Neurobiologie des Rythmes, Unité Mixte Recherche 7518, Centre National de la Recherche Scientifique/Université Louis Pasteur, Strasbourg, France
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Abstract

Melatonin, the major hormone produced by the pineal gland, displays characteristic daily and seasonal patterns of secretion. These robust and predictable rhythms in circulating melatonin are strong synchronizers for the expression of numerous physiological processes in photoperiodic species. In mammals, the nighttime production of melatonin is mainly driven by the circadian clock, situated in the suprachiasmatic nucleus of the hypothalamus, which controls the release of norepinephrine from the dense pineal sympathetic afferents. The pivotal role of norepinephrine in the nocturnal stimulation of melatonin synthesis has been extensively dissected at the cellular and molecular levels. Besides the noradrenergic input, the presence of numerous other transmitters originating from various sources has been reported in the pineal gland. Many of these are neuropeptides and appear to contribute to the regulation of melatonin synthesis by modulating the effects of norepinephrine on pineal biochemistry. The aim of this review is firstly to update our knowledge of the cellular and molecular events underlying the noradrenergic control of melatonin synthesis; and secondly to gather together early and recent data on the effects of the nonadrenergic transmitters on modulation of melatonin synthesis. This information reveals the variety of inputs that can be integrated by the pineal gland; what elements are crucial to deliver the very precise timing information to the organism. This also clarifies the role of these various inputs in the seasonal variation of melatonin synthesis and their subsequent physiological function.

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Pharmacological Reviews: 55 (2)
Pharmacological Reviews
Vol. 55, Issue 2
1 Jun 2003
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Review ArticleReview

Generation of the Melatonin Endocrine Message in Mammals: A Review of the Complex Regulation of Melatonin Synthesis by Norepinephrine, Peptides, and Other Pineal Transmitters

Valerie Simonneaux and Christophe Ribelayga
Pharmacological Reviews June 1, 2003, 55 (2) 325-395; DOI: https://doi.org/10.1124/pr.55.2.2

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Review ArticleReview

Generation of the Melatonin Endocrine Message in Mammals: A Review of the Complex Regulation of Melatonin Synthesis by Norepinephrine, Peptides, and Other Pineal Transmitters

Valerie Simonneaux and Christophe Ribelayga
Pharmacological Reviews June 1, 2003, 55 (2) 325-395; DOI: https://doi.org/10.1124/pr.55.2.2
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  • Article
    • Abstract
    • I. Introduction
    • II. Role of Melatonin
    • III. Neural and Humoral Inputs to the Mammalian Pineal Gland
    • IV. Indoleamine Metabolism in the Mammalian Pineal Gland
    • V. Noradrenergic Regulation of Melatonin Synthesis in the Mammalian Pineal Gland
    • VI. Regulation of Melatonin synthesis in the Mammalian Pineal Gland by Other Transmitters
    • VII. General Conclusions and Perspectives
    • Acknowledgments
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