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Melatonin, hormone of darkness and more – occurrence, control mechanisms, actions and bioactive metabolites

Abstract.

In its role as a pineal hormone, melatonin is a pleiotropic, nocturnally peaking and systemically acting chronobiotic. These effects are largely explained by actions via G protein-coupled membrane receptors found in the suprachiasmatic nucleus, but also in numerous other sites. Nuclear (ROR/RZR), cytoplasmic (quinone reductase-2, calmodulin, calreticulin) and mitochondrial binding sites and radical-scavenging properties contribute to the actions of melatonin. Regulation of pineal melatonin biosynthesis is largely explained by control mechanisms acting on arylalkylamine N-acetyltransferase, at the levels of gene expression and/or enzyme stability influenced by phosphorylation and interaction with 14-3-3 proteins. Melatonin is not only a hormone but is also synthesized in numerous extrapineal sites, in which it sometimes attains much higher quantities than in the pineal and the circulation. It is also present in many taxonomically distant groups of organisms, including bacteria, fungi, and plants. Moreover, melatonin is a source of bioactive metabolites, such as 5-methoxytryptamine, N 1-acetyl-N 2-formyl-5-methoxykynuramine and N 1-acetyl-5-methoxykynuramine.

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Correspondence to R. Hardeland.

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Received 2 January; received after revision 6 February 2008; accepted 8 February 2008

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Open Access This is an open access article distributed under the terms of the Creative Commons Attribution Noncommercial License ( https://creativecommons.org/licenses/by-nc/2.0 ), which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

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Hardeland, R. Melatonin, hormone of darkness and more – occurrence, control mechanisms, actions and bioactive metabolites. Cell. Mol. Life Sci. 65, 2001–2018 (2008). https://doi.org/10.1007/s00018-008-8001-x

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  • DOI: https://doi.org/10.1007/s00018-008-8001-x

Keywords.

  • AFMK
  • AMK
  • cinnoline
  • indoleamine
  • melatonin-binding site
  • 5-methoxytryptamine
  • nitric oxide
  • pineal gland