1301 Polyamines: Novel regulators of human epidermal pigmentation

The purpose of this study was to understand the impact of altered polyamine levels on epidermal pigmentation. We used laser-capture microscopy and human primary melanocyte culture to establish the mechanisms by which polyamines function and the significance of their misregulation in Melasma. The polyamines are ubiquitously expressed cations that are essential for a wide array of cellular events. Changes in intracellular polyamines can have a regulatory role in cells through control of gene expression and protein function. We show that polyamine regulator ODC1 is increased in melanocytes isolated by laser capture microscopy from melasma lesional compared to non-lesional skin. Increased ODC1 promotes increased polyamine levels and we show that the polyamine putrescine can promote TYR activity and melanogenesis in human melanocytes and in human skin organ cultures. Elevated polyamine levels drive an increase in polyamine catabolism through SAT1 and SMOX. This in turn results in the production of H202 which we propose, in part, drives melanogenesis. When polyamine catabolism is inhibited in putrescine treated cells, melanogenesis is no longer activated and pigment is decreased. We have identified a number of specific polyamine inhibitors that can block polyamine induced pigmentation in human melanocytes and skin organ cultures. Polyamine levels are altered in the skin in response to UV exposure, wounding and inflammation. Our data suggests that human epidermal melanocytes are sensitive to changes in extracellular polyamine levels and respond by modulating pigment production. Our results disclose an interesting relationship between polyamines and human skin pigmentation that could enhance our understanding of not only normal human melanogenesis/ melanin transfer but also pigmentary disorders.