Melatonin

Melatonin is a natural compound, specifically an indoleamine, produced by and found in different organisms including bacteria and eukaryotes. It was discovered by Aaron B. Lerner and colleagues in 1958 as a substance of the pineal gland from cow that could induce skin lightening in common frogs. It was subsequently discovered as a hormone released in the brain at night which controls the sleep–wake cycle in vertebrates. In vertebrates, melatonin is involved in synchronizing circadian rhythms, including sleep–wake timing and blood pressure regulation, and in control of seasonal rhythmicity including reproduction, fattening, moulting and hibernation. Many of its effects are through activation of the melatonin receptors, while others are due to its role as an antioxidant. Its primary function is to defend against oxidative stress in plants and bacteria. Mitochondria are the main cell organelles that produce the antioxidant melatonin, which indicates that melatonin is an "ancient molecule" that primarily provided the earliest cells protection from the destructive actions of oxygen. In addition to its role as a natural hormone and antioxidant, melatonin is used as a dietary supplement and medication in the treatment of sleep disorders such as insomnia and circadian rhythm sleep disorders. In humans, melatonin is a full agonist of melatonin receptor 1 (picomolar binding affinity) and melatonin receptor 2 (nanomolar binding affinity), both of which belong to the class of G-protein coupled receptors (GPCRs). Melatonin receptors 1 and 2 are both Gi/o-coupled GPCRs, although melatonin receptor 1 is also Gq-coupled. Melatonin also acts as a high-capacity free radical scavenger within mitochondria which also promotes the expression of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, glutathione reductase, and catalase via signal transduction through melatonin receptors. In animals, melatonin plays an important role in the regulation of sleep–wake cycles.