EFFECTS OF ESTROGENS ON HUMAN MELANOCYTES IN-VITRO

Subjects with elevated serum estrogen concentrations, such as those wh o are pregnant or ingesting estrogen-containing contraceptive medicati on, may develop increased skin pigmentation. As little information is available on the mechanism(s) underlying this relationship, the in vit ro effects of estrogens on melanocytes cultured from normal human skin were examined. Physiological concentrations of 17 beta-estradiol (10( -11) to 10(-9) M) significantly increased the activity of tyrosinase i n melanocytes from 15 of 23 subjects. The observed increases ranged fr om 1.2- to 2.4-fold. Melanin synthesis, which correlated with tyrosina se activity (r = 0.98, P < 0.001) was increased to a similar extent. M elanin extrusion was also increased by 17 beta-estradiol (10(-9) M). T he estrogens, estriol (10(-9) M) and estrone (10(-9) M) stimulated tyr osinase activity and melanin extrusion to a lesser extent than 17 beta -estradiol. The analogue 17 alpha-estradiol (10(-9) M) was shown to ha ve effects on melanocyte tyrosinase activity and melanin extrusion tha t were equivalent to those of 17 beta-estradiol. The pure estrogen ant agonist ICI 164384 (10(-6) M) also stimulated tyrosinase activity. Cyc loheximide (50 mu g/ml) inhibited 17 beta-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 17 alpha-analogue and a ''pure'' anti-estro gen suggest that the 17 beta-estradiol response may be mediated throug h a non-classical mechanism which is similar to that described in othe r tissues of neural crest origin.