Sensitive assay for disturbance of brain function by environmental pollutants at low concentrations

三丁基锡诱导培养大鼠海马切片细胞色素P45017α和P450arom升高。该处理还诱导睾酮和雌二醇17β的生物合成增加。由于三丁基锡可以激活RXR介导的细胞反应，我们确定了RXR对海马神经甾体生成的作用。RXR受体激动剂9-顺式维甲酸刺激大鼠海马雌二醇合成和P450 - 17α mRNA含量。这些结果表明，RXR介导了三丁基锡对海马甾体生成的作用。成年大鼠海马直接注射三丁基锡可引起P450 - 17α mRNA表达升高。然而，海马的雌二醇含量没有受到影响，尽管用三丁基锡治疗可能刺激海马的睾酮生物合成。阉割后大鼠脑及血清睾酮含量显著降低。去势大鼠海马中雌二醇含量与未处理大鼠相同。这些数据表明海马中雌二醇的含量独立于海马中睾酮的含量和合成。

Tributyltin induced increase in cytochromes P45017α and P450arom in cultures rat hippocampal slices. This treatment also induced increase in biosynthesis of testosterone and estradiol 17β. Since tributyltin can activate RXR-mediating cellular response, we determined action of RXR on neuronsteroidogenesis in the hippocampus. 9-cis Retinoic acid, an agonist for RXR, stimulated estradiol synthesis and mRNA contents for P450 17α in cultured rat hippocampus. These results indicate that the action of tributyltin on hippocampal steroidogenesis was mediated by RXR.Direct injection of tributyltin in adult rat hippocampus induced increase in mRNA for P450 17α. Estradiol content of the hippocampus, however, was not affected, although the treatment with tributyltin may stimulate testosterone biosynthesis in the hippocampus. Castration of the rat induced significant decrease in testosterone contents in brain and serum. Estradiol content in the castrated rat hippocampus was the same as that in the non-treated rat. These data indicate that the estradiol content in the hippocampus was independent from testosterone content and synthesis in the hippocampus.