Okubo T, Yokoyama Y, Kano K, Kano I
Department of Toxicology, The Tokyo Metropolitan Research Laboratory of Public Health, 3-24-1 Hyakunin-cho, Shinjuku-ku, 169-0073, Tokyo, Japan.
Food Chem Toxicol. 2001 Dec;39(12):1225-32. doi: 10.1016/s0278-6915(01)00073-4.
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 3x10(-11) M 17beta-estradiol, but at a concentration in the order of 10(5) to 10(7) higher than 17beta-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 ERalpha and an increase in that of progesterone-receptor (PR), but the effects of these parabens were not as prominent as those of 17beta-estradiol. Western blot analysis indicated that these parabens caused a slight decrease in expression of ERalpha protein. Competitive binding to human ERalpha and ERbeta 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 ERalpha and ERbeta. 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 17beta-estradiol.
通过检测雌激素受体（ER）依赖的MCF-7细胞增殖，研究了酚类防腐剂甲基对羟基苯甲酸酯、乙基对羟基苯甲酸酯、丙基对羟基苯甲酸酯、丁基对羟基苯甲酸酯、异丙基对羟基苯甲酸酯和异丁基对羟基苯甲酸酯的雌激素活性。所有这些化合物刺激细胞增殖的程度与3×10⁻¹¹ M 17β-雌二醇达到的最大细胞产量大致相同，但浓度比17β-雌二醇高10⁵至10⁷倍。对羟基苯甲酸酯的细胞增殖作用被抗雌激素ICI 182,780完全抑制。用丁基对羟基苯甲酸酯和异丁基对羟基苯甲酸酯处理的MCF-7细胞显示ERα基因表达降低，孕酮受体（PR）基因表达增加，但这些对羟基苯甲酸酯的作用不如17β-雌二醇显著。蛋白质免疫印迹分析表明，这些对羟基苯甲酸酯导致ERα蛋白表达略有下降。体外与人ERα和ERβ的竞争性结合显示，侧链较长的对羟基苯甲酸酯对雌激素受体具有更高的亲和力，并且它们对ERα和ERβ具有相似的相对结合亲和力（RBA）值。RBA值远小于己烯雌酚。总之，对羟基苯甲酸酯具有ER依赖的雌激素活性，并且它们对细胞内信号通路的影响可能与17β-雌二醇不同。
