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首页> 外文期刊>Toxicology Letters: An International Journal Providing a Forum for Original and Pertinent Contributions in Toxicology Research >Dose- and route-dependent hormonal activity of the metalloestrogen cadmium in the rat uterus
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Dose- and route-dependent hormonal activity of the metalloestrogen cadmium in the rat uterus

机译：大鼠子宫中金属雌激素镉的剂量和途径依赖性激素活性

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The toxic heavy metal cadmium (Cd) is regarded as a potential endocrine disruptor, since Cd exerts estrogen-like activity in vitro and can elicit some typical estrogenic responses in rodents upon intraperitoneal (i.p.) injection. But estrogenic effects have not been documented in vivo with other more relevant routes of exposure, although it is known that Cd absorption and distribution in the body is strongly affected by the application route. Therefore, we investigated its hormonal activity in ovariectomized Wistar rats after oral administration of CdCl_2 (0.05-4 mg/kg b.w. on 3 days by gavage and 0.4-9 mg/kg b.w. for 4 weeks in drinking water) in comparison with i.p. injection of CdCl_2 (0.00005-2 mg/kg b.w.). Uterus wet weight, height of uterine epithelium, and modulation of estrogen-regulated gene expression, i.e. uterine complement component 3 (C3), were determined, and also Cd-levels in uterus and liver were measured by atomic absorption spectrometry. The analysis revealed pronounced differences in Cd tissue levels and hormonal potency for the two routes of administration: a single i.p. injection of Cd increased dose-dependently uterine wet weight and thickness of the uterine epithelium. Interestingly, C3 mRNA expression in the uterus was down regulated at low doses of CdCl_2 (0.00005-0.05 mg/kg b.w.), but strongly stimulated at the highest dose of 2 mg/kg b.w. Other than i.p. injection, oral treatment with Cd, by gavage or in drinking water, did neither increase uterine wet weights nor epithelial thickness. But, both 3-day- and 4-week oral Cd administration resulted in a dose-dependent stimulation of C3 expression in the uterus, significant at and above 0.5 mg/kg b.w. In summary, our data demonstrate an estrogenic effect in the uterus upon i.p. injection of Cd, but considerably lower hormonal potency with oral administration: short and long-term oral treatment with Cd did not affect uterus weight or histology, whilst on the molecular level, an induction of estrogen sensitive uterine gene expression was observed, albeit at dose levels far exceeding those of dietary exposure in humans.
机译：毒性重金属镉（CD）被认为是潜在的内分泌破坏器，因为CD在体外发挥雌激素样活性，并且可以在腹膜内（I.P.）注射时引发啮齿动物中的一些典型的雌激素反应。但是，雌激素效应尚未以其他相关的暴露途径进行文件，尽管已知身体的CD吸收和分布受施加途径的强烈影响。因此，与I.P，我们在口服施用CdCl_2（0.05-4mg / kg B.W.，饮用水中的0.4-9mg / kg b.W.注射CDCl_2（0.00005-2 mg / kg B.W.）。子宫上皮的子宫湿重，高度和雌激素调节基因表达的调节，即尿嘧啶补体组分3（C3），通过原子吸收光谱法测量子宫和肝脏的CD水平。该分析显示了两种给药途径的CD组织水平和荷尔蒙效力的显着差异：单一的I.P.注射CD增加剂量依赖性子宫湿重和子宫上皮的厚度。有趣的是，子宫中的C3 mRNA表达在低剂量的CDCl_2（0.00005-0.05mg / kg B.）下调节，但在最高剂量的2mg / kg B.W中强烈刺激。除了我。注射，用CD，通过饲料或饮用水处理口服处理，既没有增加子宫湿重也没有上皮厚度。但是，3天和4周的口腔CD给药导致子宫中C3表达的剂量依赖性刺激，显着均为0.5mg / kg B.W.总之，我们的数据证明了子宫内的雌激素作用。注射CD，但与口服给药相当较低的激素效力：短期和长期口服用Cd影响子宫重量或组织学，而在分子水平上，观察到雌激素敏感子宫基因表达的诱导，尽管剂量远远超过人类膳食暴露的水平。

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