Melatonin--a pleiotropic, orchestrating regulator molecule

Melatonin, the neurohormone of the pineal gland, is also produced by various other tissues and cells. It acts via G protein-coupled receptors expressed in various areas of the central nervous system and in peripheral tissues. Parallel signaling mechanisms lead to cell-specific control and recruitmen...

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Published in:Progress in neurobiology 2011-03, Vol.93 (3), p.350-384
Main Authors: Hardeland, Rüdiger, Cardinali, Daniel P, Srinivasan, Venkatramanujam, Spence, D Warren, Brown, Gregory M, Pandi-Perumal, Seithikurippu R
Format: Article
Language:English
Subjects:
Aging - physiology
Animals
Binding Sites
Circadian Rhythm - physiology
Energy Metabolism
Humans
Immune System
Melatonin - deficiency
Melatonin - physiology
Mitochondria - metabolism
Pineal Gland - physiology
Receptors, Melatonin - metabolism
Signal Transduction - physiology
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container_issue 3
container_start_page 350
container_title Progress in neurobiology
container_volume 93
creator Hardeland, Rüdiger
Cardinali, Daniel P
Srinivasan, Venkatramanujam
Spence, D Warren
Brown, Gregory M
Pandi-Perumal, Seithikurippu R
description Melatonin, the neurohormone of the pineal gland, is also produced by various other tissues and cells. It acts via G protein-coupled receptors expressed in various areas of the central nervous system and in peripheral tissues. Parallel signaling mechanisms lead to cell-specific control and recruitment of downstream factors, including various kinases, transcription factors and ion channels. Additional actions via nuclear receptors and other binding sites are likely. By virtue of high receptor density in the circadian pacemaker, melatonin is involved in the phasing of circadian rhythms and sleep promotion. Additionally, it exerts effects on peripheral oscillators, including phase coupling of parallel cellular clocks based on alternate use of core oscillator proteins. Direct central and peripheral actions concern the up- or downregulation of various proteins, among which inducible and neuronal NO synthases seem to be of particular importance for antagonizing inflammation and excitotoxicity. The methoxyindole is also synthesized in several peripheral tissues, so that the total content of tissue melatonin exceeds by far the amounts in the circulation. Emerging fields in melatonin research concern receptor polymorphism in relation to various diseases, the control of sleep, the metabolic syndrome, weight control, diabetes type 2 and insulin resistance, and mitochondrial effects. Control of electron flux, prevention of bottlenecks in the respiratory chain and electron leakage contribute to the avoidance of damage by free radicals and seem to be important in neuroprotection, inflammatory diseases and, presumably, aging. Newly discovered influences on sirtuins and downstream factors indicate that melatonin has a role in mitochondrial biogenesis.
doi_str_mv 10.1016/j.pneurobio.2010.12.004
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subjects Aging - physiology
Animals
Binding Sites
Circadian Rhythm - physiology
Energy Metabolism
Humans
Immune System
Melatonin - deficiency
Melatonin - physiology
Mitochondria - metabolism
Pineal Gland - physiology
Receptors, Melatonin - metabolism
Signal Transduction - physiology
title Melatonin--a pleiotropic, orchestrating regulator molecule
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