Abstract
Estrogenic activities of the phenolic preservatives methylparaben, ethylparaben, propylparaben, butylparaben, isopropylparaben and isobutylparaben were examined by assaying estrogen-receptor (ER)-dependent proliferation of MCF-7 cells. All the compounds stimulated the proliferation to about the same level as the maximal cell yield attained with 3×10 −11 m 17β-estradiol, but at a concentration in the order of 10 5 to 10 7 higher than 17β-estradiol. The cell-proliferative effects of parabens were completely suppressed by anti-estrogen ICI 182,780. MCF-7 cells treated with butylparaben and isobutylparaben exhibited a decrease in gene expression of ERα and an increase in that of progesterone-receptor (PR), but the effects of these parabens were not as prominent as those of 17β-estradiol. Western blot analysis indicated that these parabens caused a slight decrease in expression of ERα protein. Competitive binding to human ERα and ERβ in vitro revealed that the parabens with longer side-chains showed greater affinity for estrogen receptors, and that they had similar relative binding affinity (RBA) values to both ERα and ERβ. RBA values were much smaller than that of diethylstilbestrol. In conclusion, parabens have ER-dependent estrogenic activities, and their effects on the intracellular signaling pathway might be different from that of 17β-estradiol.
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