Effects of PGF2α, 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 PGE(2) receptors EP1 and EP3 and the PGF(2 alpha) receptor FP, and that PGF(2 alpha) stimulates melanocyte dendricity. We now show that PGF(2 alpha) 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(2 alpha) by melanocytes. These results show that PGF(2 alpha) 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(2 alpha) in melanocytes in response to ultraviolet radiation suggest that PGF(2 alpha) could act as an autocrine factor for melanocyte differentiation. (c) 2004 Elsevier Inc. All rights reserved.