Melatonin: A Cutaneous Perspective on its Production, Metabolism, and Functions

Abstract

Melatonin, an evolutionarily ancient derivative of serotonin with hormonal properties, is the main neuroendocrine secretory product of the pineal gland. Although melatonin is best known to regulate circadian rhythmicity and lower vertebrate skin pigmentation, the full spectrum of functional activities of this free radical-scavenging molecule, which also induces/promotes complex antioxidative and DNA repair systems, includes immunomodulatory, thermoregulatory, and antitumor properties. Because this plethora of functional melatonin properties still awaits to be fully appreciated by dermatologists, the current review synthesizes the main features that render melatonin a promising candidate for the management of several dermatoses associated with substantial oxidative damage. We also review why melatonin promises to be useful in skin cancer prevention, skin photo- and radioprotection, and as an inducer of repair mechanisms that facilitate the recovery of human skin from environmental damage. The fact that human skin and hair follicles not only express functional melatonin receptors but also engage in substantial, extrapineal melatonin synthesis further encourages one to systematically explore how the skin's melatonin system can be therapeutically targeted in future clinical dermatology and enrolled for preventive medicine strategies.

Melatonin and its derivatives counteract the ultraviolet B radiation‐induced damage in human and porcine skin ex vivo

“…Therefore, we believe that the beneficial effects of melatonin application after UV exposure are real, but again would require future clinical trials. 64 In summary, melatonin or its active metabolites, including AFMK and NAS, applied before or after UVB irradiation, inhibit DNA damage, apoptosis, and oxidative stress in human and porcine skin ex vivo. Thus, exogenous, topically applied melatonin and its derivatives represent potential protective agents for preventing oxidative stress and DNA damage.…”

“…In contrast to studies of Bangha et al and Dreher et al who assessed UV‐induced erythema, our evaluation was based on the UVB‐induced changes at the epidermal/cellular levels. Therefore, we believe that the beneficial effects of melatonin application after UV exposure are real, but again would require future clinical trials …”

HMGB1 deficiency reduces H2O2‐induced oxidative damage in human melanocytes via the Nrf2 pathway

“…It was reported that locally produced protective molecules such as melatonin also act on NRF2 in protection of melanocytes. 27 Melatonin and its metabolites protect melanocytes from UVB-induced DNA damage and oxidative stress through activation of NRF2dependent pathways; these actions are independent of an effect on the classic membrane melatonin receptors. 28 Melatonin and its derivatives counteract the ultraviolet B radiation-induced damage in human and porcine skin ex vivo.…”

Melatonin promotes secondary hair follicle development of early postnatal cashmere goat and improves cashmere quantity and quality by enhancing antioxidant capacity and suppressing apoptosis

“…The skin has the capacity to produce glucocorticoids in a regulated fashion which served as the response of skin to stress . In addition, it has been well demonstrated that the skin and the skin cells can intrinsically produce melatonin and metabolize melatonin . Melatonin ( N ‐acetyl‐5‐methoxytryptamine) is a naturally multifunctional molecule which is synthesized in the pineal gland of vertebrates and various tissues and organs including retina, bone marrow, gastrointestinal, placenta, testes, and ovary .…”