Effects of PGF_2α on human melanocytes and regulation of the FP receptor by ultraviolet radiation

Prostaglandins are potent lipid hormones that activate multiple signaling pathways resulting in regulation of cellular growth, differentiation, and apoptosis. In the skin, prostaglandins are rapidly released by keratinocytes following ultraviolet radiation and are chronically present in inflammatory skin lesions. We have shown previously that melanocytes, which provide photoprotection to keratinocytes through the production of melanin, express several receptors for prostaglandins, including the PGE₂ receptors EP₁ and EP₃ and the PGF_2α receptor FP, and that PGF_2α stimulates melanocyte dendricity. We now show that PGF_2α stimulates the activity and expression of tyrosinase, the rate-limiting enzyme in melanin synthesis. Analysis of FP receptor regulation showed that the FP receptor is regulated by ultraviolet radiation in melanocytes in vitro and in human skin in vivo. We also show that ultraviolet irradiation stimulates production of PGF_2α by melanocytes. These results show that PGF_2α binding to the FP receptor activates signals that stimulate a differentiated phenotype (dendricity and pigmentation) in melanocytes. The regulation of the FP receptor and the stimulation of production of PGF_2α in melanocytes in response to ultraviolet radiation suggest that PGF_2α could act as an autocrine factor for melanocyte differentiation.