F3 EXPRESSION OF ESTROGEN RECEPTORS IN CUTANEOUS MELANOCYTES AND THEIR POTENTIAL ROLE IN THE REGULATION OF PIGMENT CELL PHENOTYPE
Meskiri AN, Thornton MJ, Tobin DJ
Medical Biosciences, School of Life Sciences, University of Bradford, United Kingdom

Several cutaneous pigmentary changes have been associated with altered sex hormone levels in women, particularly during pregnancy. Furthermore, epidemiological studies suggest that females have a survival benefit with metastatic melanoma. The recent identification of a second estrogen receptor (ER b), has revealed greater potential in the diversity of estrogen action in skin biology. However, estrogen action in human pigment cell biology remains poorly characterized. This study was designed to assess whether the expression of ER a and ER b, the androgen receptor (AR) and aromatase differed in melanocytes isolated from the hair follicle (HFMc) versus the epidermis (EMc), using fully matched cultures (i.e. from same donor/skin site). Moreover, the expression of these markers was also assessed as a function of pigment level in pigmented (FM94) and non-pigmented melanoma (FM55) cell lines Finally, the effect of increasing cAMP levels (via IBMX stimulation, 10-4M), with its associated stimulation of pigment cell differentiation, was assessed in FM55 melanoma cells. Results suggested that cultured HFMc express higher levels of ER b and aromatase peptides compared to matched EMc. Moreover, the degree of pigment in melanoma cells correlated positively with the level of ER b and aromatase expression, such that higher expression levels were observed in FM94 melanoma cells compared to FM55 melanoma cells. Finally, the induction of pigmentation in poorly pigmented FM55 melanoma cells (via the IBMX-induced increase in cAMP levels) correlated positively with increased expression of ER a, ER b, AR and aromatase. These findings suggest that pigment cell phenotype (e.g. melanogenesis) may be regulated by estrogen signalling via ER b. Moreover, the apparently higher level of receptor expression in HFMc compared to EMc may indicate that follicular and epidermal melanocytes are differentially responsive to sex steroids. Future studies will examine whether steroid hormone binding can affect the differentiation of different cutaneous melanocyte subpopulations.