Department of Biology, Norwegian University of Science and Technology (NTNU), Høgskoleringen 5, 7491 Trondheim, Norway.
Environ Toxicol Pharmacol. 2005 Nov;20(3):485-92. doi: 10.1016/j.etap.2005.05.008. Epub 2005 Jul 11.
Using the European common frog, Rana temporaria, as a model, we have studied the organ-specific gene expression patterns of thyroid hormone receptor isoforms after exposure to an organochlorine (OC) compound, p,p'-DDE. Four groups of frogs were subcutaneously injected with p,p'-DDE at 0.01, 0.1, 1 and 10mg/kg body weight, respectively. In addition, one group, serving as the control group, was injected with pure corn oil. TH receptor isoforms (TRα and TRβ) gene expressions were evaluated in the brain, kidney, testis and liver using real-time PCR with gene-specific primers. Our results show that p,p'-DDE doses induced slight elevations of TRα and TRβ mRNA in the brain. In the testis, p,p'-DDE induced an initial significant 3-fold increase of TRα mRNA at 0.01mg/kg and thereafter clear dose-dependent decreases of TRα mRNA levels were observed. For testicular TRβ mRNA levels, p,p'-DDE induced a slight elevation at 0.01mg/kg and thereafter significant decreases in TRβ mRNA levels were observed. p,p'-DDE induced significant 2-4-fold elevations of both TR isoforms in frog kidney. The strongest transcriptional effect of p,p'-DDE on TR isoforms was observed in the kidney. While TRα mRNA was not measurable in the liver, p,p'-DDE induced an initial 1.7-fold increase at 0.01mg/kg of TRβ mRNA and thereafter an apparent dose-dependent decrease was observed. The relative abundance of TRα and TRβ gene expression in different organs are in the order: kidney>testis>brain>liver. While the induction TRα and TRβ might result to hypersensitivity and subsequent gain of biological functions, the inhibition might result to loss of biological function. Given the high persistency in the environment and continued use in developing countries coupled with the tendency for global atmospheric transport, DDT and its metabolites such as p,p'-DDE will remain a focus of concern both for scientific and societal reasons.
以欧洲普通蛙（Rana temporaria）为模型，我们研究了甲状腺激素受体异构体在暴露于有机氯化合物（OC）化合物 p,p'-DDE 后的器官特异性基因表达模式。将四组青蛙分别用 0.01、0.1、1 和 10mg/kg 体重的 p,p'-DDE 皮下注射，另外一组作为对照组，注射纯玉米油。使用基因特异性引物的实时 PCR 评估了脑中、肾脏、睾丸和肝脏中的 TH 受体异构体（TRα 和 TRβ）基因表达。我们的结果表明，p,p'-DDE 剂量在脑中引起 TRα 和 TRβ mRNA 的轻微升高。在睾丸中，p,p'-DDE 在 0.01mg/kg 时诱导 TRα mRNA 最初显著增加 3 倍，此后观察到 TRα mRNA 水平的明显剂量依赖性降低。对于睾丸 TRβ mRNA 水平，p,p'-DDE 在 0.01mg/kg 时诱导轻微升高，此后观察到 TRβ mRNA 水平明显降低。p,p'-DDE 在青蛙肾脏中诱导两种 TR 异构体均显著增加 2-4 倍。p,p'-DDE 对 TR 异构体的转录效应最强在肾脏中观察到。虽然在肝脏中无法测量到 TRα mRNA，但 p,p'-DDE 在 0.01mg/kg 时诱导 TRβ mRNA 最初增加 1.7 倍，此后观察到明显的剂量依赖性降低。不同器官中 TRα 和 TRβ 基因表达的相对丰度顺序为：肾脏>睾丸>大脑>肝脏。虽然 TRα 和 TRβ 的诱导可能导致过敏和随后获得生物学功能，但抑制可能导致生物学功能丧失。鉴于 DDT 及其代谢物如 p,p'-DDE 在环境中的高持久性以及在发展中国家的持续使用，加上全球大气传输的趋势，它们将继续成为科学和社会关注的焦点。
