Diethylstilbestrol (DES) is a synthetic estrogen and proven human teratogen and carcinogen reported to act via the estrogen receptor α (ERα). Since the endogenous ERα ligand 17β-estradiol (E2) does not show these adverse effects to a similar extent, we hypothesized that DES’ interaction with the ERα differs from that of E2. The current study aimed to investigate possible differences between DES and E2 using in vitro assays that detect ERα-mediated effects, including ERα-mediated reporter gene expression, ERα-mediated breast cancer cell (T47D) proliferation and ERα-coregulator interactions and gene expression in T47D cells. Results obtained indicate that DES and E2 activate ERα-mediated reporter gene transcription and T47D cell proliferation in a similar way. However, significant differences between DES- and E2-induced binding of the ERα to 15 coregulator motifs and in transcriptomic signatures obtained in the T47D cells were observed. It is concluded that differences observed in binding of the ERα with several co-repressor motifs, in downregulation of genes involved in histone deacetylation and DNA methylation and in upregulation of CYP26A1 and CYP26B1 contribute to the differential effects reported for DES and E2.

己烯雌酚 (DES) 是一种合成雌激素，据报道经证实可通过雌激素受体 α (ERα) 发挥作用的人类致畸剂和致癌物。由于内源性 ERα 配体 17β-雌二醇 (E2) 没有显示出类似程度的这些不利影响，我们假设 DES 与 ERα 的相互作用不同于 E2。目前的研究旨在使用体外检测来研究 DES 和 E2 之间的可能差异，这些检测检测 ERα 介导的效应，包括 ERα 介导的报告基因表达、ERα 介导的乳腺癌细胞 (T47D) 增殖和 ERα-调节因子相互作用和基因表达。 T47D 细胞。获得的结果表明 DES 和 E2 以类似的方式激活 ERα 介导的报告基因转录和 T47D 细胞增殖。然而，观察到 DES 和 E2 诱导的 ERα 与 15 个共调节子基序的结合以及在 T47D 细胞中获得的转录组学特征之间的显着差异。得出的结论是，在 ERα 与几个共阻遏基序的结合、参与组蛋白去乙酰化和 DNA 甲基化的基因的下调以及 CYP26A1 和 CYP26B1 的上调中观察到的差异有助于报告对 DES 和 E2 的不同影响。