Melatonin—A pleiotropic, orchestrating regulator molecule

Abstract

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.

Melatonin as potential candidate to prevent the toxicity induced by chemical warfare agents

“…Melatonin is also involved in several and important functions such as vasomotor control and adrenal function, possesses antiexcitatory actions, regulates immune function and energy metabolism, including anti-inflammatory properties (Hardeland et al 2011). Melatonin is highly lipophilic and consequently study, it has been reported that in vivo oxidative stress production, accompanied by increasing oxidative stress markers after mustard gas exposure, was counteracted by melatonin administration (Pohanka et al 2011).…”

Male-female differences in 6-sulfatoxymelatonin excretion in hypopituitary patients

“…Even if the most well known function of melatonin in human beings is its contribution to synchronization of biologic rhythms, with a key role in light-dark cycles, an important body of evidence in recent years has suggested that melatonin may be involved in other functions, including body temperature modulation, antiproliferative effects, antioxidant effects, interrelationship with the immune system, etc. (16)(17)(18)(19)(20)(21)(22), also acting as a "neuroendocrine transducer" of information collected from the environment (23). IGFBP3, may also be influenced by circadian genes.…”

Intense blue light therapy during the night-time does not suppress the rhythmic melatonin biosynthesis in a young boy

“…Melatonin has pleiotropic eff ects acting at diff erent levels of the human physiology (Hardeland et al 2011). Th erefore, the decreased melatonin production can be related to diff erent pathological situations and requires a specifi c attention.…”