Abstract

Objectives: 1. Understand role of polyamine in skin pigmentation 2. The novel ;pathway of polyamines in the pathogenesis of melasma 3. Polyamine inhibitors in the management of melasma Introduction: Melasma is a chronic disfiguring condition and can be difficult to treat. Current treatment options are directed at inhibiting the tyrosinase pathway. Uncovering new pathways in pathogenesis of melasma is essential for the development of new effective treatments. In this lecture, 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 Materials / method: 1. Polyamine enzyme ODC1 was found to be elevated in melanocytes in lesional skin of patients with melasma as compared to perilesional skin 2. Invitro experiments using melanocyte, keratinocyte/melanocyte cultures to demonstrate the effects of polyamine and pigmentation 3. Invitro experiments elucidating the mechanisms of pigment induction in polyamine pathways 4. Clinical trial of polyamine inhibitor as compared to 4% hydroquinone in the management of melasma. Results: In melasma, we found that polyamine regulator ODC1 is upregulated in melanocytes from lesional skin. Further investigation revealed that polyamine can promote pigmentation in human explants and primary melanocytes through induction of tyrosinase. Polyamine supplementation on normal epidermal melanocytes results in the activation of polyamine catabolism, which results in increased intracellular H2O2 while inhibition of polyamine catabolism prevents polyamine-induced promotion of tyrosinase levels. Finally a clinical trial showed the polyamine inhibitor is as effective as hydroquinone in melasma Conclusion: Polyamines play an important role in skin homeostasis, especially in skin pigmentation. Interventions directed at this pathway will open up new avenues in the management of skin pigmentary disorders.