Melatonin in the skin: synthesis, metabolism and functions

Melatonin, a ubiquitous methoxyindole, is produced by and metabolized in the skin. Melatonin affects skin functions and structures through actions mediated by cell-surface and putative-nuclear receptors expressed in skin cells. Melatonin has both receptor-dependent and receptor-independent effects that protect against oxidative stress and can attenuate ultraviolet radiation-induced damage. The widespread expression and pleiotropic activity of the cutaneous melatoninergic system provides for a high level of cell-specific selectivity. Moreover, intra-, auto- and para-crine mechanisms equip this system with exquisite functional selectivity. The properties of endogenous melatonin suggest that this molecule is an important effector of stress responses in the skin. In this way, melatonin actions may counteract or buffer both environmental and endogenous stressors to maintain skin integrity.

Introduction

The strategic location of the skin as a key barrier between the environment and the internal milieu renders it a crucial instrument of preserving body homeostasis, yet also exposes it to numerous pathological agents, processes and events. Thus, the capability to locally recognize, discriminate and integrate specific signals within a highly heterogeneous environment and to launch appropriate responses immediately is a vital property of the skin [1]. These skin functions are integrated into the skin immune, pigmentary, epidermal and adnexal systems and are in continuous communication with the central immune, neural and endocrine signaling systems 1, 2, 3, 4, 5.

Coordination among these local and systemic responses is mediated by the skin neuroendocrine system 1, 2, which uses local equivalents of the hypothalamo–pituitary–adrenal axis, catecholaminergic, cholinergic, steroidogenic and secosteroidogenic systems. Given their common embryonal origins, it is not surprising that the skin shares numerous mediators with the CNS and endocrine system. Recent research has revealed that mammalian skin also harbors a complex melatoninergic system, whose role in the maintenance of cutaneous homeostasis is explored here. Unlike the pineal melatoninergic system, its intracutaneous counterpart is exposed directly to numerous environmental stressors, such as ultraviolet radiation (UVR), the importance of which is reviewed here.