Melatonin in Dermatology
Abstract
Introduction Melatonin, derived from serotonin and primarily secreted by the pineal gland, regulates circadian rhythms and influences pigmentation.[1,2] In humans, it acts as an antioxidant and supports DNA repair, while being synthesized in various tissues, including skin, liver, and kidney, to maintain cellular health and homeostasis.[3,4] Intracutaneous Melatonin Metabolic Pathways Melatonin production in the skin involves four key steps [Figure 1]:[4] Tryptophan is converted to 5-hydroxytryptophan (5-OH-Trp) by tryptophan hydroxylase. 5-OH-Trp is transformed into serotonin by aromatic amino acid decarboxylase. Serotonin is acetylated to form N-acetylserotonin (NAS). NAS is converted to melatonin via hydroxyindole-O-methyltransferase, which can remain in the skin or enter the bloodstream. Figure 1: Melatonin synthesisMelatonin acts through G protein-coupled melatonin receptor 1 (MT1) and MT2 receptors or nuclear Retinoic Acid Receptor-related Orphan Receptor (RZR/ROR), enhancing antioxidant enzyme activity and promoting glutathione synthesis. Its lipophilicity enables effective transcutaneous absorption, reducing apoptosis by inhibiting caspases (Caspases 3 and 9) involved in cell death.[5,6] Pharmacokinetics Melatonin is rapidly absorbed after oral administration and has a short half-life of about 45 minutes to 1 hour. It is metabolized primarily in the liver and excreted in the urine. Melatonin levels in the body exhibit a circadian rhythm, with peak levels typically…
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