Review

Cellular and Molecular Life Sciences

, Volume 71, Issue 16, pp 2997-3025

Extrapineal melatonin: sources, regulation, and potential functions

  • Darío Acuña-CastroviejoAffiliated withInstituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de GranadaDepartamento de Fisiología, Facultad de Medicina, Universidad de GranadaUnidad de Gestión Clínica de Laboratorios, Hospital Universitario San Cecilio Email author 
  • , Germaine EscamesAffiliated withInstituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de GranadaDepartamento de Fisiología, Facultad de Medicina, Universidad de Granada
  • , Carmen VenegasAffiliated withInstituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de GranadaDepartamento de Fisiología, Facultad de Medicina, Universidad de Granada
  • , María E. Díaz-CasadoAffiliated withInstituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de GranadaDepartamento de Fisiología, Facultad de Medicina, Universidad de Granada
  • , Elena Lima-CabelloAffiliated withInstituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de GranadaDepartamento de Fisiología, Facultad de Medicina, Universidad de Granada
  • , Luis C. LópezAffiliated withInstituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la Salud, Universidad de GranadaDepartamento de Fisiología, Facultad de Medicina, Universidad de Granada
  • , Sergio Rosales-CorralAffiliated withDepartment of Cellular and Structural Biology, University of Texas Health Science Center
  • , Dun-Xian TanAffiliated withDepartment of Cellular and Structural Biology, University of Texas Health Science Center
  • , Russel J. ReiterAffiliated withDepartment of Cellular and Structural Biology, University of Texas Health Science Center

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Abstract

Endogenous melatonin is synthesized from tryptophan via 5-hydroxytryptamine. It is considered an indoleamine from a biochemical point of view because the melatonin molecule contains a substituted indolic ring with an amino group. The circadian production of melatonin by the pineal gland explains its chronobiotic influence on organismal activity, including the endocrine and non-endocrine rhythms. Other functions of melatonin, including its antioxidant and anti-inflammatory properties, its genomic effects, and its capacity to modulate mitochondrial homeostasis, are linked to the redox status of cells and tissues. With the aid of specific melatonin antibodies, the presence of melatonin has been detected in multiple extrapineal tissues including the brain, retina, lens, cochlea, Harderian gland, airway epithelium, skin, gastrointestinal tract, liver, kidney, thyroid, pancreas, thymus, spleen, immune system cells, carotid body, reproductive tract, and endothelial cells. In most of these tissues, the melatonin-synthesizing enzymes have been identified. Melatonin is present in essentially all biological fluids including cerebrospinal fluid, saliva, bile, synovial fluid, amniotic fluid, and breast milk. In several of these fluids, melatonin concentrations exceed those in the blood. The importance of the continual availability of melatonin at the cellular level is important for its physiological regulation of cell homeostasis, and may be relevant to its therapeutic applications. Because of this, it is essential to compile information related to its peripheral production and regulation of this ubiquitously acting indoleamine. Thus, this review emphasizes the presence of melatonin in extrapineal organs, tissues, and fluids of mammals including humans.

Keywords

Melatonin receptors Oxidative stress Free radicals Mitochondria Cytoprotection Homeostasis