Ramdhan Doni Hikmat, Ito Yuki, Yanagiba Yukie, Yamagishi Nozomi, Hayashi Yumi, Li ChunMei, Taneda Shinji, Suzuki Akira K, Watanabe Gen, Taya Kazuyoshi, Kamijima Michihiro, Nakajima Tamie
Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Japan.
Toxicol Lett. 2009 Dec 15;191(2-3):103-8. doi: 10.1016/j.toxlet.2009.08.013. Epub 2009 Aug 20.
We previously reported that exposure to low (22.5+/-0.2 nm in diameter, 15.4+/-1.0 microg/m(3) in mass weight, 2.27x10(5)/cm(3) in mean number concentration), and medium (26.1+/-0.5 nm, 36.4+/-1.2 microg/m(3), 5.11x10(5)/cm(3)) concentrations of nanoparticle-rich diesel exhaust (NR-DE) for 1 and 2 months (5 h/day, 5 days/week) significantly increased plasma testosterone in male Fischer 344 rats, whereas exposure to a high concentration (27.1+/-0.5 nm, 168.8+/-2.7 microg/m(3), 1.36x10(6)/cm(3)) did not. The present study attempts to clarify the mechanism of this elevation. Low and medium exposures to NR-DE for 1 and 2 months significantly increased steroidogenic acute regulatory protein (StAR)- and cytochrome P450 side-chain cleavage (P450scc)-mRNA and their protein expressions in the testis of rats, in which the elevation pattern was very similar to that of plasma testosterone levels. Interestingly, both exposure levels for 1 month significantly increased growth hormone (GH) receptor expression in the testis, and low exposure also increased testicular insulin-like growth factor I-mRNA levels and hepatic microsomal cytochrome P450 2C11-mRNA and their protein levels in rats. These two factors are thought to be related to growth hormone secretion. Disruption of testosterone biosynthesis by NR-DE exposure may be a mode of action for reproductive toxicity, which may, in part, be regulated by increasing StAR and P450scc expressions via GH signalling.
我们之前报道过，雄性Fischer 344大鼠暴露于低浓度（直径22.5±0.2纳米，质量浓度15.4±1.0微克/立方米，平均数量浓度2.27×10⁵/立方厘米）和中浓度（26.1±0.5纳米，36.4±1.2微克/立方米，5.11×10⁵/立方厘米）的富含纳米颗粒的柴油机尾气（NR-DE）中1个月和2个月（每天5小时，每周5天），会显著提高其血浆睾酮水平，而暴露于高浓度（27.1±0.5纳米，168.8±2.7微克/立方米，1.36×10⁶/立方厘米）则不会。本研究旨在阐明这种升高的机制。低浓度和中浓度暴露于NR-DE 1个月和2个月，会显著增加大鼠睾丸中类固醇生成急性调节蛋白（StAR）和细胞色素P450侧链裂解酶（P450scc）的mRNA及其蛋白表达，其升高模式与血浆睾酮水平非常相似。有趣的是，1个月的两种暴露水平均显著增加了睾丸中生长激素（GH）受体的表达，低浓度暴露还增加了大鼠睾丸中胰岛素样生长因子I的mRNA水平以及肝微粒体细胞色素P450 2C11的mRNA及其蛋白水平。这两个因素被认为与生长激素分泌有关。NR-DE暴露导致的睾酮生物合成中断可能是生殖毒性的一种作用方式，这可能部分是通过GH信号通路增加StAR和P450scc的表达来调节的。
