Baikal seals (Pusa sibirica) are vulnerable to high levels of organic pollutants. Here, we evaluated the transactivation potencies of bisphenols (BPs) and hydroxylated polychlorinated biphenyls (OH-PCBs) via the Baikal seal estrogen receptor α and β (bsERα and bsERβ) using in vitro and in silico approaches. In vitro reporter gene assays showed that most BPs and OH-PCBs exhibited estrogenic activity with bsER sub-type-specific potency. Among the BPs tested, bisphenol AF showed the lowest EC₅₀ for both bsERs. 4′-OH-CB50 and 4′-OH-CB30 showed the lowest EC₅₀ among OH-PCBs tested for bsERα and bsERβ, respectively. 4-((4-Isopropoxyphenyl)-sulfonyl)phenol, 4′-OH-CB72, and 4′-OH-CB121 showed weak bsERα-specific transactivation. Only 4-OH-CB107 did not affect both bsERs. In silico docking simulations revealed the binding affinities of these chemicals to bsERs and partially explained the in vitro results. Using the in silico simulations and molecular descriptors as explanatory variables and the in vitro results as objective variables, the quantitative structure-activity relationship (QSAR) models constructed for classification and regression accurately separated bsER-active compounds from non-active compounds and predicted the in vitro bsERα- and bsERβ-transactivation potencies, respectively. The QSAR models also suggested that chemical polarity, van der Waals surface area, bridging atom structure, position of the phenolic-OH group, and ligand interactions with key residues of the ligand binding pocket are critical variables to account for the bsER transactivation potency of the test compounds. We also succeeded in constructing computational models for predicting in vitro transactivation potencies of mouse ERs in the same manner, demonstrating the applicability of our approach independent of species-specific responses.

贝加尔海豹（Pusa sibirica）很容易受到高浓度有机污染物的影响。在这里，我们使用体外和计算机方法评估了双酚 (BP) 和羟基化多氯联苯 (OH-PCB) 通过贝加尔海豹雌激素受体 α 和 β（bsERα 和 bsERβ）的反式激活效力。体外报告基因测定表明，大多数 BP 和 OH-PCB 表现出雌激素活性，并具有 bsER 亚型特异性效力。在测试的 BP 中，双酚 AF的两种 bsER 的EC ₅₀最低。在bsERα和bsERβ测试的OH-PCB中，4'-OH-CB50和4'-OH-CB30分别显示出最低的EC _{50 。}4-((4-异丙氧基苯基)-磺酰基)苯酚、4'-OH-CB72 和 4'-OH-CB121 显示出较弱的 bsERα 特异性反式激活。只有 4-OH-CB107 不影响两种 bsER。计算机对接模拟揭示了这些化学物质与 bsER 的结合亲和力，并部分解释了体外结果。使用计算机模拟和分子描述符作为解释变量，体外结果作为目标变量，为分类和回归构建的定量构效关系（QSAR）模型准确地将bsER活性化合物与非活性化合物分开，并预测了in分别为体外bsERα-和bsERβ-反式激活效力。QSAR 模型还表明，化学极性、范德华表面积、桥接原子结构、酚-OH 基团的位置以及配体与配体结合袋关键残基的相互作用是解释 bsER 反式激活效力的关键变量。测试化合物。我们还成功地构建了以相同方式预测小鼠 ER体外反式激活效力的计算模型，证明了我们的方法的适用性，独立于物种特异性反应。