Testicular cytochrome P450scc and LHR as possible targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the mouse
Testicular cytochrome P450scc and LHR as possible targets of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in the mouse
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DOI：
10.1016/j.mce.2004.02.005
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发表时间：
2004-06-30
影响因子：
4.1
通讯作者：
Tohyama, C
中科院分区：
文献类型：
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作者：
Fukuzawa, NH;Ohsako, S;Tohyama, C
据报道，成年动物暴露于2,3,7,8-四氯二苯并-对二恶英（TCDD）会干扰睾丸中甾体生成的调节，可能是由芳烃受体（AhR）引起的。为了阐明AhR是如何参与睾丸甾体生成的，我们使用野生型和无AhR的雄性小鼠进行了对比实验，这些小鼠腹腔注射了TCDD。TCDD给药野生型小鼠睾丸中P450scc和LHR水平显著降低，而ahr缺失小鼠睾丸中P450scc和LHR水平不变。为了比较合成雌激素激动剂雌二醇-3-苯甲酸酯（EB）在下丘脑-垂体-性腺（HPG）轴上的抗雄激素特性。小鼠垂体中LHalpha/FSHalpha、LHbeta、FSHbeta和GnRHR基因的表达严重受损，而tcdd处理小鼠未观察到任何影响。此外，eb处理小鼠睾丸中LHR基因的表达增加。这些观察结果表明，TCDD的靶点与EB在HPG轴上的靶点不同，TCDD治疗以ahr依赖的方式抑制睾丸中的P450scc和LHR基因。2004爱思唯尔爱尔兰有限公司版权所有。
Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in adult animals has been reported to perturb the regulation of steroidogenesis in the testis, possibly by arylhydrocarbon receptor (AhR). To clarify how AhR is involved in the testicular steroidogenesis, we carried out comparative experiments using wild-type and AhR-null male mice that were intraperitoneally administered TCDD. The TCDD administration to wild-type mice showed significant reduction of P450scc and LHR in the testis, whereas the levels in the AhR-null Mouse testis were unchanged. To compare anti-androgenic properties on hypothalamo-pituitary-gonadal (HPG) axis, estradiol-3-benzoate (EB), a synthetic estrogen agonist. was administered to mice, the expression of the LHalpha/FSHalpha, LHbeta, FSHbeta and GnRHR genes was severely impaired in the pituitary gland, in contrast to no observed effects in the TCDD-treated mice. In addition, the expression of the LHR gene was increased in the testis of the EB-treated mice. These observations suggest that the target of TCDD is different from that of EB on HPG axis and that TCDD treatment suppresses the P450scc and LHR genes in the testis in an AhR-dependent manner. (C) 2004 Elsevier Ireland Ltd. All rights reserved.