Melatonin is a hormone, and it was first discovered in 1958 by Dr Aaron Lerner, an American physician at Yale University School of medicine. It is secreted by the pineal gland, which is a small endocrine gland located within the brain. Tissue samples from the pineal glands of animals was found to alter melanin pigmentation in frogs, which caused melanin aggregation. This observation gave rise to the name melatonin1.
What is less commonly known, is that melatonin is also produced in tiny amounts in the retina and in the gastrointestinal tract2. Because melatonin is mostly secreted at night, and due to its involvement in signalling the “time of the day” it has become known as a Zeitgeber, which means “time cue” in German. Melatonin is also sometimes referred to as the “hormone of darkness”.
Here is a flowchart summarising the pathway for the biosynthesis of melatonin3:
Darkness stimulates the pineal gland to secrete melatonin. Exposure to light supresses the secretion of melatonin4.
Interestingly, melatonin receptors have been found in a number of organs throughout the body including in the retina, cardiovascular system, liver, gallbladder, intestines, kidneys, prostate, breast epithelial cells, ovaries, adipocytes (fat cells) and the skin5. Melatonin has also been found in the seeds and leaves of plants, in concentrations that are much higher than night time levels found in humans6.
Melatonin acts on 2 receptors called MT1 and MT2. Melatonin is an antioxidant, although it is best known for its role in the promotion of sleep through its actions on a structure in the brain called the suprachiasmatic nucleus (SCN).
1. McCord C, Allen FP. Evidences associating pineal gland function of alterations in pigmentation. SO J Exptl Zool. 1917;23:207.
2. Principles and Practice of Sleep Medicine, sixth edition, Kryger, Roth and Dement
3. Grivas TB, Savvidou OD. Melatonin the “light of night” in human biology and adolescent idiopathic scoliosis. Scoliosis. 2007 Apr 4;2:6. doi: 10.1186/1748-7161-2-6. PMID: 17408483; PMCID: PMC1855314
4. Hardeland R. Chronobiology of Melatonin beyond the Feedback to the Suprachiasmatic Nucleus-Consequences to Melatonin Dysfunction. Int J Mol Sci. 2013 Mar 12;14(3):5817-41. doi: 10.3390/ijms14035817. PMID: 23481642; PMCID: PMC3634486.
5. Ekmekcioglu C. Melatonin receptors in humans: biological role and clinical relevance. Biomed Pharmacother. 2006 Apr;60(3):97-108. doi: 10.1016/j.biopha.2006.01.002. Epub 2006 Feb 20. PMID: 16527442.
6. Pandi-Perumal SR, Srinivasan V, Maestroni GJ, Cardinali DP, Poeggeler B, Hardeland R. Melatonin: Nature’s most versatile biological signal? FEBS J. 2006 Jul;273(13):2813-38. doi: 10.1111/j.1742-4658.2006.05322.x. PMID: 16817850.
7. Masters A, Pandi-Perumal SR, Seixas A, Girardin JL, McFarlane SI. Melatonin, the Hormone of Darkness: From Sleep Promotion to Ebola Treatment. Brain Disord Ther. 2014;4(1):1000151. doi: 10.4172/2168-975X.1000151. PMID: 25705578; PMCID: PMC4334454