HEAT SHOCK PROTEINS IN SERTOLI CELL TOXICITY

多种抑制男性药物毒性的生化机制 生育率在很大程度上是未知的。二溴氯丙烷、镉 氯化物(Cd)和甲氧基乙醇会抑制精子数量。DBCP、CD和MA (甲氧基乙酸乙酯，甲氧基乙醇的有毒代谢物)改变生化 应用于支持细胞原代培养时的功能终点。 由于支持细胞在形态和生化上为 哺乳动物睾丸中的精子发生，抑制支持细胞的药物 这种功能预计会降低男性的生育力。CD导致 两种低分子量蛋白质的合成及磷酸化 已被鉴定为热休克蛋白的支持细胞。这 Proposal检验了热休克的诱导 睾丸细胞的反应是热应激机制中的关键步骤。 以及化学诱导的精子发生抑制。该化合物的合成 小分子热休克蛋白及其磷酸化和转录 它们的mrna将被测定并与生化相关。 暴露于DBCP、CD和MA的大鼠支持细胞培养的改变。 将使用原位杂交来定位合成的位置 DBCP、MA和Cd染毒大鼠睾丸中的小分子热休克蛋白。 这也将允许低分子量热休克的联系。 蛋白质在生殖细胞选择性丧失的部位和阶段。

The biochemical mechanism of toxicity of many agents that inhibit male fertility are largely unknown. Dibromochloropropane (DBCP), cadmium chloride (Cd) and methoxyethanol depress sperm counts. DBCP, Cd and MA (methoxyacetate, the toxic metabolite of methoxyethanol) alter biochemical endpoints of function when applied to primary cultures of Sertoli cells. Since Sertoli cells provide morphological and biochemical support for spermatogenesis in the mammalian testes, agents that inhibit Sertoli cell function would be expected to depress male fertility. Cd causes the synthesis and phosphorylation of two low molecular weight proteins by Sertoli cells that have been identified as heat shock proteins. This proposal examines the hypothesis that the induction of the heat shock response in testicular cells is a critical step in the mechanism of heat - and chemical-induced inhibition of spermatogenesis. The synthesis of the small heat shock proteins, their phosphorylation and the transcription of their mRNA will be determined and correlated with the biochemical alterations noted in rat Sertoli cell cultures exposed to DBCP, Cd and MA. In situ hybridization will be used to localize the site of synthesis of the small heat shock proteins in the testis of rats exposed to DBCP, MA and Cd. This will also allow the association of low molecular weight heat shock proteins when sites and stages of selective loss of germ cells.