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  • It has previously been shown that human melanocytes


    It has previously been shown that human melanocytes are responsive to a multiplicity of hormonal triggers [10], particularly to pituitary or ovarian hormones [11]. Studies concerning the effects of Senegenin receptor on human melanocytes led to inconsistent data [12], [13]. Im et al. [14] reported that the response to hormones is donor specific: Estrogen and progesterone increased cell numbers and tyrosinase activity in melanocytes from three of eight donors. By contrast, two studies demonstrated that progesterone did not increase tyrosinase activity [11], [15] and even decreased melanin content [15]. In a Senegenin receptor study that examined the influence of endocrine factors on the gene expression of melanocortin 1 receptor, which is one of the key genes for melanin synthesis, progesterone had no effect on the mRNA level [16]. After exposure to sunlight or UVB irradiation, melanocytes develop more dendrites, contain more melanosomes and show a higher degree of melanization [17]. Furthermore, a dose-dependent decrease in cell counts but an increase in tyrosinase activity and melanin content were noted after UVB [18], UVA or mixed UVA+UVB irradiation [19].
    Materials and methods
    Discussion To evaluate the influence of the progestogen components in contraceptives on the development of pigmentary disorders in women, we studied the effects of progesterone and CMA on proliferation and pigment formation of human melanocytes in vitro. As reported previously, 17β-estradiol led to a significant increase in melanocyte proliferation [12]. However, this stimulatory effect was only seen in approximately half of the experiments. This variance could be due to donor-dependent differences as suggested previously [14]. Distinct mechanisms that may explain the interindividual differences in responses are still unknown but could possibly comprise different expression patterns of nuclear activators and repressors. Progesterone and CMA at a concentration of 100 nM reduced the proliferation rate of melanocytes, while they had no significant effect on tyrosinase activity. These results stand in contrast with the findings of Im et al. [14] that progesterone increased proliferation and tyrosinase activity of melanocytes. As in our study, cells were treated with progesterone at a concentration of 100 nM for a total of 6 days; however, the growth medium contained additional components, such as α-melanocyte-stimulating hormone, α-tocopherol and penicillin–streptomycin, and the melanocytes were plated at a higher density. Similar to our observations, it was shown in two further studies that addition of progesterone did not increase tyrosinase activity [11], [15] and even decreased melanin content [15], while the proliferation rate was not mentioned. Concomitant UVA or UVB irradiation of hormone-exposed melanocytes was performed in a subgroup of experiments. A minimal increase in proliferation of melanocytes treated with 17β-estradiol and irradiated with UV was observed when compared with cells without irradiation (n.s.). In contrast, proliferation rates of melanocytes treated with progestogens were lower when irradiated with UVA and higher when irradiated with UVB compared with mock-irradiated cells (n.s.). Different effects on tyrosinase activity of melanocytes were not observed for 17β-estradiol and progestogens with or without UV irradiation. According to the literature, UV radiation of melanocytes leads to a dose-dependent decrease in cell counts but to an increase in tyrosinase activity and melanin content [17], [18], [19]. Our findings may be explained by differences in the irradiation protocol. Single doses in our experiments were much higher than those in comparable studies that used either longer irradiation periods or higher irradiation frequencies. Perhaps these irradiation protocols more efficiently induce pigment formation in melanocytes. However, in the study by Ramirez-Bosca et al. [18], a marked increase in tyrosinase activity could be found only after irradiation with 200 mJ/cm2 of UVB, which was considerably higher than the cumulative doses used in our experiments.