CULTURED HUMAN MELANOCYTES RESPOND TO MSH PEPTIDES AND ACTH

Although the administration of melanocyte-stimulating hormone (MSH) pe ptides results in skin darkening in man, cultured human melanocytes ha ve been reported to be unresponsive to these peptides. This may be a c onsequence of the conditions under which the cells were maintained in vitro, particularly the use of phorbol esters and cholera toxin as mel anocyte mitogens. By culturing the cells in the absence of these addit ives, we demonstrate that a-MSH and its synthetic analogue Nle(4)DPhe( 7) alpha-MSH (NDP-MSH) induce dose-related increases in melanin conten t and tyrosinase activity and affect cell morphology in the majority o f human melanocyte cultures. In addition, NDP-MSH induces increases in tyrosinase mRNA and tyrosinase-related protein-1 (TRP-1) mRNA. The do se-response curves for the MSH peptides are sigmoidal and the two pept ides are equipotent in their effects on human melanocytes. Adrenocorti cotropic hormone (ACTH) also affects morphology and stimulates melanog enesis and tyrosinase activity in human melanocytes. However, the dose -response curves for ACTH are biphasic, and the melanocytes respond to lower concentrations of ACTH than MSH peptides, similar to those norm ally present in human plasma. These findings may be important in under standing the role of these pro-opiomelanocortin peptides in human skin pigmentation.