Fax +41 61 306 12 34 E-Mail karger@karger.ch www.karger.com Original Paper Dermatology 2012;224:168–176 DOI: 10.1159/000338023 Expression Profile of Genes Associated with the Dopamine Pathway in Vitiligo Skin Biopsies and Blood Sera Ene Reimann a, b, d Külli Kingo b Maire Karelson b Paula Reemann a, b Ulvi Loite b Maris Keermann b Kristi Abram b Eero Vasar a, c Helgi Silm b Sulev Kõks a, c, d a Department of Physiology, b Department of Dermatology and Venereology and c Center of Translational Medicine, University of Tartu, and d Institute of Veterinary Medicine and Animal Sciences, Estonian University of Life Sciences, Tartu, Estonia Introduction Vitiligo is an acquired skin disorder where melano- cytes are selectively destroyed, causing white patches on the skin. There is no clear explanation of the causes of vitiligo pathogenesis, however the disease has most often been described to have an autoimmune etiology. Other hypotheses include melanocyte self-destruction through oxidative stress, lack of essential cytokines derived from keratinocytes and effect of cytotoxical mediators from peripheral nerve endings [1–3]. Melanogenesis is under complex regulatory control by multiple agents interacting via different pathways. These modifying agents are not organized through simple lin- ear sequence, but rather a multidimensional network. The most important regulator for melanogenesis is the melanocortin pathway, where melanocortin receptor 1 with its ligands promotes and agouti protein inhibits me- lanogenesis [4]. There is considerable evidence that the melanocortin system is functionally linked with the dopamine system [5]. Dopaminergic compounds inhib- it the secretion of -melanocyte-stimulating hormone ( -MSH) and -endorphin and affect pro-opiomelano- cortin mRNA expression level in the pituitary [6, 7]. Clas- sically catecholamines (dopamine, norepinephrine and Key Words Vitiligo  Gene expression  Protein expression  Dopamine pathway  Melanocytes Abstract Background: Dopamine has been proven to be toxic for me- lanocytes. In vitiligo patients the level of dopamine is in- creased and the functioning of several enzymes participat- ing in the dopamine pathway is changed. Methods: With the use of quantitative real-time polymerase chain reaction and ELISA the expression of genes connected to the dopamine pathway (PAH, PCD, TH, DDC, DBH, PNMT, GPX1, MAOA, MAOB, COMT, DRD1–DRD5, VMAT1 and VMAT2) was observed in viti- ligo patients’ and control subjects’ skin and blood. Results: The mRNA expression of GPX1 , DDC, MAOA, DRD1 and DRD5 differs in vitiligo skin and the protein level of DDC, MAOA, MAOB, DRD1 and DRD5 is changed in vitiligo patients’ skin and/or blood sera. Conclusions: The dopamine pathway probably influences melanogenesis directly or through the melanocortin pathway. We provide new data about changes of expression profile of the dopamine-synthesizing enzyme DDC, the dopamine-degrading enzymes MAOA and MAOB and the D1-like family dopamine receptors in vitiligo skin and blood sera. Copyright © 2012 S. Karger AG, Basel Received: January 13, 2012 Accepted after revision: March 13, 2012 Published online: May 4, 2012 Sulev Kõks, MD, PhD Department of Physiology, University of Tartu 19 Ravila Street EE–50411 Tartu (Estonia) Tel. +372 7 374 335, E-Mail sulev.koks  @  ut.ee © 2012 S. Karger AG, Basel 1018–8665/12/2242–0168$38.00/0 Accessible online at: www.karger.com/drm