648 Long-term melatonin treatment stimulates human epidermal pigmentation and melanocyte number

Abstract

Melatonin, the evolutionarily ancient methoxyindoleamine, has long captured the attention of investigators since the discovery of its regulation of mammalian fur and amphibian skin pigmentation, as well as its extrapineal synthesis and receptor expression in human skin. Yet, melatonin’s role in human skin and its impact on melanocyte physiology remain unclear. Therefore, we asked whether melatonin stimulates or inhibits epidermal pigmentation through its effects on melanin content, tyrosinase activity, as well as melanocyte number and proliferation in their natural cutaneous habitat with interactions with surrounding keratinocytes, at 2 different time points (three and six days of culture) and concentrations (50, 100, and 200 ug/mL). Our preliminary data show that after three days of culture, melatonin tendentially decreases tyrosinase activity in a dose-dependent manner and tendentially decreases the number of proliferative melanocytes without affecting the number of melanocytes present in the epidermis. Interestingly, after six days of culture, the different concentrations of melatonin decrease the in situ tyrosinase activity. However, melatonin increases intraepidermal melanin content correlated with an increased number of melanocytes. However, after six days of culture, melatonin at 200 ug/mL stimulated melanocyte proliferation. Taken together, our data showed that melatonin’s regulatory effects on epidermal pigmentation and melanocyte number and their proliferation ex vivo, are depending on the concentration used and the duration of treatment. Short-term pulse therapy with inexpensive hormone promises to target hyperpigmentary cutaneous disorders while long-term therapy at high concentration may help treating hypopigmentary cutaneous disorders such as vitiligo by increasing the intracutaneous pool of melanocytes and restoring a physiological level of pigmentation.