Extrapineal Melatonin: Location and Role within Diffuse Neuroendocrine System

During the last decade, much attention has centred on melatonin, one of the hormones of the diffuse neuroendocrine system. For many years it was considered to be only a hormone of the pineal gland. As soon as highly sensitive antibodies to indolealkylamines became available, melatonin was identified not only in pineal gland, but also in extrapineal tissues. These included the retina, Harderian gland, gut mucosa, cerebellum, airway epithelium, liver, kidney, adrenals, thymus, thyroid, pancreas, ovary, carotid body, placenta and endometrium. It has also been localized in non-neuroendocrine cells such as mast cells, natural killer cells, eosinophilic leukocytes, platelets and endothelial cells. This list of cells indicates that melatonin has a unique position among the hormones of the diffuse neuroendocrine system. It is found in practically all organ systems. Functionally, melatonin-producing cells are part and parcel of the diffuse neuroendocrine system as a universal system of response, control and organism protection. Taking into account the large number of such melatonin-producing cells in many organs, the wide spectrum of biological activities of melatonin and especially its main property as a universal regulator of biological rhythms, it is now possible to consider extrapineal melatonin as a key paracrine signal molecule for the local co-ordination of intercellular relationships.