Effects of estrogens on human melanocytes in vitro

Abstract

Subjects with elevated serum estrogen concentrations, such as those who are pregnant or ingesting estrogen-containing contraceptive medication, may develop increased skin pigmentation. As little information is available on the mechanism(s) underlying this relationship, the in vitro effects of estrogens on melanocytes cultured from normal human skin were examined. Physiological concentrations of 17β-estradiol (10 −11 to 10 −9 M) significantly increased the activity of tyrosinase in melanocytes from 15 of 23 subjects. The observed increases ranged from 1.2- to 2.4-fold. Melanin synthesis, which correlated with tyrosinase activity ( r = 0.98, P < 0.001) was increased to a similar extent. Melanin extrusion was also increased by 17β-estradiol (10 −9 M). The estrogens, estriol (10 −9 M) and estrone (10 −9 M) stimulated tyrosinase activity and melanin extrusion to a lesser extent than 17β-estradiol. The analogue 17α-estradiol (10 −9 M) was shown to have effects on melanocyte tyrosinase activity and melanin extrusion that were equivalent to those of 17β-estradiol. The pure estrogen antagonist ICI 164384 (10 −6 M) also stimulated tyrosinase activity. Cycloheximide (50 μg/ml) inhibited 17β-estradiol-induced tyrosinase stimulation ( P < 0.001). These results indicate that several aspects of melanocyte function respond directly to estrogenic stimulation. The equivalent effects of the 17α-analogue and a “pure” anti-estrogen suggest that the 17β-estradiol response may be mediated through a non-classical mechanism which is similar to that described in other tissues of neural crest origin.