Development of risk assessment system for human by environmental disruptants using nuclear hormone receptor

内分泌干扰物被认为对不同的器官有不同的影响。利用过表达人雌激素受体的真核细胞和酵母分析了内分泌干扰物对雌激素的反应。在野生动物中，海鸥等受到大量环境污染物污染的物种出现甲状腺增生和甲状腺肿瘤。为了研究内分泌干扰物对甲状腺激素系统的影响，构建并分析了组成型过表达甲状腺激素受体的HeLaTR细胞。用含有甲状腺激素反应元件的质粒作为增强剂转染HeLaTR细胞，通过添加T3诱导荧光素酶活性。双酚A和邻苯二甲酸2-二乙基己酯均能与雌激素受体结合，对荧光素酶活性无影响，但羟基化PCB抑制了添加T3引起的荧光素酶活性。相反，二恶英增强了荧光素酶的活性，但单独二恶英对荧光素酶的活性没有影响。这些结果提示HeLaTR细胞可以作为内分泌干扰物作用甲状腺激素的工具。

Endocrine disruptants are thought to have various effects on various organs. Estrogenic responses by endocrine disruptants were analyzed using eukaryotic cells and yeast, which are overexpressing human estrogen receptors. In wildlife, some species such as seagulls contaminated with large amount of environmental pollutants showed thyroid hyperplasia and thyroid tumors. To address the effects on thyroid hormone system by endocrine disruptants, the HeLaTR cells that constitutively overexpressed thyroid hormone receptor were constructed and analyzed. Luciferase activity was induced by the addition of T3 in HeLaTR cells transfected with the plasmid containing thyroid hormone response element as an enhancer. Bisphenol A and 2-diethylhexyl phtalate, both could bind to estrogen receptor, had no effect on the luciferase activity, but hydroxylated PCB repressed the luciferase activity caused by the addition of T3. In contrast, dioxin enhanced the luciferase activity, however dioxin alone caused no effect on the activity. These results suggested that HeLaTR cells could be used as the tool for thyroid hormone action by endocrine disruptants.