Cellular and Molecular Life Sciences

, Volume 71, Issue 16, pp 2997–3025 | Cite as

Extrapineal melatonin: sources, regulation, and potential functions

  • Darío Acuña-CastroviejoEmail author
  • Germaine Escames
  • Carmen Venegas
  • María E. Díaz-Casado
  • Elena Lima-Cabello
  • Luis C. López
  • Sergio Rosales-Corral
  • Dun-Xian Tan
  • Russel J. Reiter


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.


Melatonin receptors Oxidative stress Free radicals Mitochondria Cytoprotection Homeostasis 



This study was partially supported by grants from the Instituto de Salud Carlos III (RD12/0043/0005, PI08-1664), and from the Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía (P07-CTS-03135 and CTS-101), Spain. ED is a fellow from the Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía, Spain.


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Copyright information

© Springer Basel 2014

Authors and Affiliations

  • Darío Acuña-Castroviejo
    • 1
    • 2
    • 3
    Email author
  • Germaine Escames
    • 1
    • 2
  • Carmen Venegas
    • 1
    • 2
  • María E. Díaz-Casado
    • 1
    • 2
  • Elena Lima-Cabello
    • 1
    • 2
  • Luis C. López
    • 1
    • 2
  • Sergio Rosales-Corral
    • 4
  • Dun-Xian Tan
    • 4
  • Russel J. Reiter
    • 4
  1. 1.Instituto de Biotecnología, Centro de Investigación Biomédica, Parque Tecnológico de Ciencias de la SaludUniversidad de GranadaGranadaSpain
  2. 2.Departamento de Fisiología, Facultad de MedicinaUniversidad de GranadaGranadaSpain
  3. 3.Unidad de Gestión Clínica de LaboratoriosHospital Universitario San CecilioGranadaSpain
  4. 4.Department of Cellular and Structural BiologyUniversity of Texas Health Science CenterSan AntonioUSA

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