Responsiveness of the adult male rat reproductive tract to 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure: Ah receptor and ARNT expression, CYP1A1 induction, and Ah receptor down-regulation.
Responsiveness of the adult male rat reproductive tract to 2,3,7,8-tetrachlorodibenzo-p-dioxin exposure: Ah receptor and ARNT expression, CYP1A1 induction, and Ah receptor down-regulation.
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DOI：
10.1006/taap.1998.8388
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发表时间：
1998-06
影响因子：
3.8
通讯作者：
B. L. Roman;R. Pollenz;R. Peterson
中科院分区：
文献类型：
--
作者：
B. L. Roman;R. Pollenz;R. Peterson
在成年期、胎儿晚期和出生后早期暴露于2，3，7，8-四氯二苯并-p-二恶英（TCDD）会对雄性大鼠生殖系统产生多种不良影响。因此，确定雄性大鼠生殖器官和这些器官中可能是TCDD暴露的直接目标的细胞类型是有意义的。由于TCDD毒性可能是由TCDD/芳烃受体（AhR）/AhR核转运蛋白（ARNT）复合物介导的基因转录改变的结果，因此使用蛋白质印迹法检查了成年男性生殖道各器官中AhR和ARNT的存在。在检查的所有器官（睾丸、附睾、输精管、腹侧前列腺、背外侧[结合背侧和外侧]前列腺和精囊）中均可检测到这两种蛋白。虽然技术上的困难排除了免疫组织化学评价AhR在这些器官中的分布，ARNT是本地化在所有器官中的各种细胞类型，包括生殖细胞，上皮细胞，成纤维细胞，平滑肌细胞和内皮细胞。亚细胞定位在器官和这些器官内的细胞类型之间变化。为了确定TCDD暴露是否会改变这些器官中的基因表达，动物被给予TCDD（25 μ g/kg po）或溶剂，并在24 h处以安乐死，并评价细胞色素P4501 A1（CYP 1A 1）表达。通过Western印迹，只有腹侧和背外侧前列腺表现出显着的诱导CYP 1A 1。免疫组化证实了这种诱导和本地化的CYP 1A 1表达的前列腺腹侧叶和侧叶的上皮细胞。免疫组织化学还显示，在附睾和精囊的选择上皮细胞，以及输精管和精囊的内皮细胞CYP 1A 1诱导。在睾丸中未观察到诱导。最后，AhR和ARNT表达TCDD暴露和对照动物进行了评估，通过蛋白质印迹。结果显示，TCDD暴露对ARNT蛋白表达没有影响，而在所有检查的器官中，AhR表达降低至对照的5-51%。总之，AhR和ARNT都在检查的成年雄性大鼠生殖道的所有器官中表达，并且这些器官（睾丸除外）中的上皮和/或内皮细胞对CYP 1A 1诱导方面的TCDD暴露有反应。此外，所有组织表现出显着减少AhR蛋白质含量后，TCDD暴露，不相关的CYP 1A 1反应的幅度。
Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) either in adulthood or during late fetal and early postnatal development causes a variety of adverse effects on the male rat reproductive system. It was therefore of interest to identify male rat reproductive organs and cell types within these organs that might be direct targets of TCDD exposure. Because TCDD toxicity could possibly be the result of alterations in gene transcription mediated by the TCDD/aryl hydrocarbon receptor (AhR)/AhR nuclear translocator (ARNT) complex, the presence of the AhR and ARNT in the various organs of the adult male reproductive tract was examined using Western blotting. Both proteins were detectable in all organs examined (testis, epididymis, vas deferens, ventral prostate, dorsolateral [combined dorsal and lateral] prostate, and seminal vesicle). Although technical difficulties precluded the immunohistochemical evaluation of AhR distribution in these organs, ARNT was localized in all organs in a variety of cell types, including germ cells, epithelial cells, fibroblasts, smooth muscle cells, and endothelial cells. Subcellular localization varied across organs and across cell types within these organs. In order to determine whether TCDD exposure could alter gene expression in these organs, animals were dosed with TCDD (25 micrograms/kg po) or vehicle and euthanized at 24 h, and cytochrome P4501A1 (CYP1A1) expression was evaluated. By Western blotting, only the ventral and dorsolateral prostates exhibited significant induction of CYP1A1. Immunohistochemistry confirmed this induction and localized CYP1A1 expression to epithelial cells of the ventral and lateral lobes of the prostate. Immunohistochemistry also revealed CYP1A1 induction in select epithelial cells in the epididymis and seminal vesicle, as well as endothelial cells in the vas deferens and seminal vesicle. No induction was observed in the testis. Finally, AhR and ARNT expression in TCDD-exposed and control animals was evaluated by Western blotting. Results revealed no effect of TCDD exposure on ARNT protein expression, while AhR expression was decreased to 5-51% of control in all organs examined. In summary, both AhR and ARNT were expressed in all organs of the adult male rat reproductive tract examined, and epithelial and/or endothelial cells within each of these organs (with the exception of the testis) were responsive to TCDD exposure in terms of CYP1A1 induction. In addition, all tissues exhibited marked reductions in AhR protein content after TCDD exposure that did not correlate with the magnitude of the CYP1A1 response.