Unresponsiveness of human epidermal melanocytes to melanocyte-stimulating hormone and its association with red hair

There is increasing evidence that pro-opiomelanocortin-derived peptides have a role in controlling human skin pigmentation. In vitro, human epidermal melanocytes respond to melanocyte-stimulating hormone (MSH) with increases in melanogenesis and cell dendricity. However, in the present study, not all melanocyte cultures exhibited these changes and 24% were totally unresponsive to MSH. This unresponsiveness was limited to melanocytes from white Europeans but was particularly prevalent in cultures from individuals with red hair. Cyclic AMP: the second messenger of the melanocyte-associated MSH (MC-I) receptor, induced melanocyte dendricity, even in those cultures which were morphologically unresponsive to MSH. The cyclic nucleotide also increased melanogenesis in the cultures that responded melanogenically to MSH bur its effect was reduced in those cultures that were unresponsive to MSH. Thus, while the morphological data support the hypothesis that unresponsiveness is mediated at the MSH receptor. intracellular events may also be important in determining melanogenic unresponsiveness to MSH.