Human melanogenesis is stimulated by diacylglycerol

The intracellular signal pathways that mediate pigmentation in human skin are unknown. We now report that a diacylglycerol (DAG) analogue 1-oleoyl-2-acetyl-glycerol (OAG) 25-100 microns strikingly increased the melanin content of cultured human melanocytes in a dose dependent manner without altering growth rate. The pigment increase occurred within 24 h, was accompanied by increased incorporation of the melanin precursor L-3,4-dihydroxyphenyl alanine (DOPA), required new protein synthesis, and was completely blocked by the protein kinase C (PKC) inhibitors H-7 and sphingosine. A PKC-inactive DAG isomer had no effect on melanin per cell. These results implicate protein kinase C and its effector DAG in melanogenesis.