Hyperpigmentary conditions can arise when melanogenesis in the epidermis is misregulated. Understanding the pathways underlying melanogenesis is essential for the development of effective treatments. Here, we report that a group of metabolites called polyamines are important in the control of melanogenesis in human skin. Polyamines are cationic molecules present in all cells and are essential for cellular function. We report that polyamine regulator ODC1 is upregulated in melanocytes from melasma lesional skin. We report that the polyamine putrescine can promote pigmentation in human skin explants and primary normal human epidermal melanocytes through induction of tyrosinase which is rate-limiting for the synthesis of melanin. Putrescine supplementation on normal human epidermal melanocytes results in the activation of polyamine catabolism, which results in increased intracellular H₂O_2. Polyamine catabolism is also increased in human skin explants that have been treated with putrescine. We further report that inhibition of polyamine catabolism prevents putrescine-induced promotion of tyrosinase levels and pigmentation in normal human epidermal melanocytes, showing that polyamine catabolism is responsible for the putrescine induction of melanogenesis. Our data showing that putrescine promotes pigmentation has important consequences for hyperpigmented and hypopigmented conditions. Further understanding of how polyamines control epidermal pigmentation could open the door for the development of new therapeutics.

当表皮中的黑色素生成失调时，就会出现色素沉着过度的情况。了解潜在的黑色素生成途径对于开发有效的治疗方法至关重要。在这里，我们报道了一组称为多胺的代谢产物在控制人类皮肤黑色素生成中很重要。多胺是存在于所有细胞中的阳离子分子，对细胞功能至关重要。我们报告说，多胺调节剂ODC1在黄褐斑病变皮肤的黑素细胞中被上调。我们报告说，多胺腐胺可以通过诱导酪氨酸酶来促进人皮肤外植体和主要的正常人表皮黑色素细胞中的色素沉着，酪氨酸酶是限制黑色素合成的速率。在正常人表皮黑素细胞上补充腐胺会激活多胺分解代谢，₂ O2 _。已经用腐胺治疗的人皮肤外植体中多胺分解代谢也增加了。我们进一步报道，多胺分解代谢的抑制作用阻止了腐胺诱导的酪氨酸酶水平的促进和正常人表皮黑素细胞的色素沉着，表明多胺分解代谢是腐胺诱导黑素生成的原因。我们的数据表明，腐胺可促进色素沉着，对色素沉着和色素沉着的状况具有重要的影响。对多胺如何控制表皮色素沉着的进一步理解可能为新疗法的开发打开大门。