Melatonin: Basic and clinical aspect

Abstract

Melatonin (MEL), the “hormone of darkness,” is an indolamine mainly secreted at night by the pineal gland. It is also synthesized by other tissues, being the enterochromaffin cells the most important extrapineal sites. The ubiquity, pleiotropy, and complexity are the three terms that summarize the properties and actions of MEL. Two well-characterized enzymes participate in its synthesis: N-acetyltransferase, the first-rate limiting enzyme in MEL production, which converts serotonin to N-acetylserotonin (NAS), and hydroxyindole-O-methyltransferase, which converts NAS to MEL. Most of the MEL’s actions are mediated by membrane (MT1 and MT2) and nuclear (ROR/RZR) receptors. However, some MEL effects seem to be independent of the involvement of receptors or related to Ca2+-binding proteins. The signal transduction pathways triggered by MEL involve the AC/cAMP/PKA/CREB, phospholipase C (PLC)-β and PLC-η, and Rafs/MEK1/2/ERK1/2 cascades. MEL participates in the circadian rhythms, the modulation of season changes, in reproduction, as well as an antioxidant, antiapoptotic, anti-inflammatory, oncostatic, and anticonvulsant drug. Exogenous MEL is employed in a number of physiopathological conditions, mainly for the treatment of sleep disorders and jet lag. The antioxidant properties of MEL have been proven to be beneficial to patients with rheumatoid arthritis, females with infertility, elderly patients with primary essential hypertension, and multiple sclerosis patients. The spectrum of the uses of MEL seems to be wide, although more investigation is needed in order to know better the molecular mechanisms and the possible side effects.