Melatonin is a naturally occurring substance produced by the pineal gland located in the brains of mammals. It is, by definition, a hormone and has been found to be involved in circadian rhythms - those inner cycles that tell all mammals when to sleep and when to wake. Melatonin is a hormone produced by the pineal gland, which is located just beneath the center of the brain. Melatonin is also manufactured synthetically and used as a supplement. Melatonin is synthesized from tryptophan and is the major hormone produced by the pineal gland. The melatonin when taken as a supplement is synthetically manufactured. Melatonin is also available in foods such as milk, peanuts, almonds, turkey and chicken but in insignificant amounts.
Melatonin is synthesized endogenously by the pinealocytes of the pineal gland. The essential amino acid L-tryptophan is a precursor in the synthesis of melatonin. In this synthesis, L-tryptophan first gets metabolized to 5-hydroxytryptophan from which 5-hydroxytryptamine, also known as serotonin, is made. 5-hydroxytryptamine is converted to melatonin in a two-step process, occurring mainly in the pineal gland. Melatonin is also known as N-acetyl-5-methoxytryptamine and N-[2-(5-Methoxy-1H-indol-3-yl) ethyl] acetamide.
Melatonin is derived in pinealocytes from L-tryptophan. 5-hydroxytryptamine or serotonin is an intermediate in the biosynthetic process. The rate limiting step in the synthesis of melatonin is the n-acetylation of the 5-hydroxytryptamine by the enzyme arylalkylamine N-acetyltransferase (AA-NAT). Melatonin synthesis displays a circadian rhythm that is reflected in serum melatonin levels. The rhythm is generated by a circadian clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus. The SCN clock is set to the 24 hour day by the natural light-dark cycle. Light signals through a direct retinal pathway to the SCN. The SCN clock sends circadian signals over a neural pathway to the pineal gland. This drives rhythmic melatonin synthesis. The neural input to the gland is norepinephrine, and the output is melatonin. Specifically, the rhythm of the enzyme AA-NAT is under SCN control, with the resulting melatonin rhythm characterized by high levels at night. Thus, the synthesis and release of melatonin are stimulated by darkness and inhibited by light. The effects of hormones are typically mediated through receptors. Two forms of high-affinity melatonin receptors and one form of a low-affinity receptor have been identified. The high-affinity ML1 receptors are designated Mel1a and Mel1b. The low-affinity receptor is designated ML2.
The Mel1a receptor is expressed in the SCN and in the hypophyseal pars tuberalis. The SCN is the putative site of circadian action of melatonin, and the hypophyseal pars tuberalis is the putative site of its reproductive effects. The Mel1b receptor is expressed mainly in the retina. The ML1 melatonin receptors belong to the family of guanadine triphosphate-binding proteins or G protein-coupled receptors. Activation of the ML1 receptors results in inhibition of adenylate cyclase activity in target cells.
Melatonin may be indicated for some forms of insomnia and other sleep disturbances. Research results are mixed with respect to claims that melatonin can abolish some of the symptoms of jet lag. Use of the supplement in cancer and immune disorders is unsupported by current research; there are some promising findings, but they are very preliminary. There is no evidence to substantiate claims that melatonin can delay aging, be useful in cardiovascular disease, depression, seasonal affective disorder or sexual dysfunction. Melatonin may be used to treat insomnia, delayed sleep phase syndrome, fibromyalgia, or jet lag. Melatonin is a hormone secreted at night by the pineal gland of the brain. Melatonin is a very short-acting substance, remaining in the body only a few hours. Melatonin's main use has been to regulate sleep and circadian rhythms and allow the individual to feel more refreshed and alert the following day. As melatonin is directly involved with sleep regulation, the supplement's use in the treatment of age-related sleep disorders, jet lag or shift work is impressive. Furthermore, melatonin has also been shown to improve the condition of Seasonal Affected Disorder (SAD) and extend the life span of animals. This hormone is involved in setting the timing (entrainment) of mammalian circadian rhythms, as well as regulating seasonal responses to changes in day length in seasonally breeding mammals—so called photoperiodic responses. Photoperiodic responses include changes in reproductive status, behavior and body weight. Seasonal effects on reproduction in humans are subtle, and the role of melatonin here, if any, is unclear. Recently, melatonin supplementation has become popular as a possible aid for sleep disorders among other things.