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

三丁基锡诱导培养的大鼠海马片细胞色素P45017α和P450arom增加。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在海马神经元类固醇生成中的作用。RXR激动剂9-顺式维甲酸可促进培养的大鼠海马神经元雌激素合成和P45017α的表达。这些结果表明，三丁基锡对大鼠海马类固醇合成的作用是通过RXR介导的。成年大鼠海马区直接注射三丁基锡可诱导P45017α基因表达增加。然而，尽管三丁基锡治疗可能会刺激海马体中睾酮的生物合成，但海马体中雌二醇的含量并未受到影响。去势后大鼠脑和血清中睾酮含量显著降低。去势大鼠海马区雌二醇含量与未治疗组相同。这些数据表明，海马区的雌二醇含量与海马区的睾酮含量和合成无关。

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.