Differential effects of melatonin as a broad range UV-damage preventive dermato-endocrine regulator

Abstract

Melatonin or N-acetyl-5-methoxytryptamine, is a compound derived from tryptophan that is found in all organisms from single cells to vertebrates and the human. It is one of the most evolutionarily conserved and pleiotropic hormone still active in humans and has been implicated in vital skin functions such as hair growth, fur pigmentation as well as melanoma control. Being a main secretory product of the pineal gland, melatonin regulates seasonal biorhythms, reproductive mechanisms or mammary gland metabolism. Due to its wide range endocrine properties it is also recognized to modulate numerous additional functions ranging from scavenging free radicals, immunomodulation-mediated DNA repair, wound healing, involvement in gene expression connected with circadian clocks and modulation of secondary endocrine signaling including prolactin release. Recently, apart from above mentioned entities, it was shown that melatonin suppresses ultraviolet (UV)-induced damage in human skin and human derived cell lines (e.g., keratinocytes, fibroblasts). The magnitude of UV-induced damage is mediated apparently by various molecular mechanisms related to generation of reactive oxygen species (ROS), apoptosis and mitochondrial-mediated cell death which are all counteracted or modulated by melatonin. We provide here an update of the relevant protective effects and molecular mechanisms of action of melatonin in the skin.

Keywords: antioxidant; apoptosis; melatonin; mitochondria; oxidative stress; skin; ultraviolet radiation.

Figure 1

Biosynthesis pathway of melatonin in the skin. Melatonin is synthesized from tryptophan in a cascade of enzymatic reactions catalyzed by tryptophan hydroxylase (TPH), amino acid decarboxylase (AAD), arylalkylamine N-acetyltransferase (AANAT), arylamine N-acetyltransferase (NAT) and hydroxyindole-O-methyltransferase (HIOMT).

Figure 2

Oxidative stress-induced melatonin response. Melatonin and its metabolites AFMK and/or AMK are found to significantly protect against oxidative damage by scavenging ROS (direct activity) or enhancing gene and activity expression of the main antioxidant enzymes (GPx, CAT, SOD) via nuclear (RORα), membrane (MT1, MT2) and cytosolic (NQO2/MT3) receptors (indirect activity).