CATECHOL-O-METHYLTRANSFERASE IN VITILIGO

Catechol-O-methyltransferase (COMT) is involved in the metabolism of n eurotransmitters such as epinephrine, norepinephrine and dopamine. For melanocytes, the enzyme is of particular importance in preventing the formation of toxic o-quinones during melanin synthesis. It has been s uggested that COMT plays a regulatory role in melanin synthesis. Indee d, when the melanin precursor molecule DHI(2C) is methylated by COMT i t is no longer available for incorporation into melanin. Auto-destruct ion by intermediates of melanin metabolism has been implicated in the aetiology of vitiligo. Therefore enzyme activities in vitiligo patient s and in healthy controls mere compared. Systemic COMT activities were measured using red blood cells (RBC) as starting material. However, a s local alterations in COMT activity may be specifically involved in v itiligo, the enzyme activity was also measured in epidermal homogenate s. Finally, to ascribe epidermal COMT activity to the responsible cell type(s), enzyme activity was measured in cultured vitiligo non-lesion al melanocytes and melanocytes from healthy controls as well as in cul tured keratinocytes from lesional skin and in purified keratinocytes f rom control skin. It was found that epidermal homogenates from vitilig o patients expressed higher levels of COMT activity than homogenates f rom healthy controls. Such differences were not found at the systemic level (i.e. in RBC) nor could they be explained by measurements on sep arately cultured epidermal cell types, indicating that the COMT activi ty was induced at the tissue level by extracellular factors. It is pos sible that elevated levels of catecholamines secreted by keratinocytes or by nerve endings in vitiliginous skin in close proximity to the ep idermis cause damage to all epidermal cells, an effect which is insuff iciently neutralized by elevated levels of COMT activity. Catecholamin es may well be more damaging to the melanocytes than to the keratinocy tes because of their slower turnover rate.