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海洋硬骨鱼类(真鲷)中硫脲类的致甲状腺肿效率。

The goitrogenic efficiency of thioamides in a marine teleost, sea bream (Sparus auratus).

机构信息

CCMAR, CIMAR, Laboratório Associado, Universidade do Algarve, Campus de Gambelas, 8005-139 Faro, Portugal.

出版信息

Gen Comp Endocrinol. 2012 Dec 1;179(3):369-75. doi: 10.1016/j.ygcen.2012.09.022. Epub 2012 Sep 29.

Abstract

Studies on the role of thyroid hormones (THs) in teleost fish physiology have deployed the synthetic goitrogens, methimazol (MMI), propilthiouracil (PTU) and thiourea (TU) that are used to treat human hyperthyroidism. However, the action of the goitrogens, MMI, PTU and TU at different levels of the hypothalamic-pituitary-thyroid (HPT) axis in teleosts is largely unknown. The central importance of the hypothalamus and pituitary in a number of endocrine regulated systems and the cross-talk that occurs between different endocrine axes makes it pertinent to characterize the effects of MMI, PTU and TU, on several endpoints of the thyroid system. The marine teleost, sea bream (Sparus auratus) was exposed to MMI, PTU and TU (1mg/kg wet weight per day), via the diet for 21days. Radioimmunoassays (RIA) of plasma THs and ELISA of the TH carrier transthyretin (TTR) revealed that MMI was the only chemical that significantly reduced plasma TH levels (p<0.05), although both MMI and PTU significantly (p<0.05) reduced plasma levels of circulating TTR (p<0.05). Histological analysis of the thyroid tissue revealed modifications in thyrocyte activity that explain the reduced circulating levels of THs. MMI also significantly (p<0.05) up-regulated transcript abundance of liver deiodinase 1 and 2 while significantly (p<0.05) decreasing TRβ expression in the pituitary, all hallmarks of HPT axis action of goitrogens in vertebrates. The results indicate that in the sea bream MMI is the most effective goitrogen followed by PTU and that TU (1mg/kg wet weight for 21days) failed to have a goitrogenic effect. The study highlights the non-uniform effect of goitrogens on the thyroid axis of sea bream and provides the basis for future studies of thyroid disrupting pollutants.

摘要

在鱼类生理学研究中,甲状腺激素(THs)的作用已通过使用合成致甲状腺肿剂甲巯咪唑(MMI)、丙基硫氧嘧啶(PTU)和硫脲(TU)来治疗人类甲状腺功能亢进。然而,这些致甲状腺肿剂在鱼类下丘-垂体-甲状腺(HPT)轴的不同水平上的作用在很大程度上是未知的。下丘脑和垂体在许多内分泌调节系统中的核心重要性以及不同内分泌轴之间的相互作用,使得表征 MMI、PTU 和 TU 对甲状腺系统的几个终点的影响具有相关性。海洋鱼类真鲷(Sparus auratus)通过饮食暴露于 MMI、PTU 和 TU(每天 1mg/kg 湿重)21 天。用放射免疫测定(RIA)和酶联免疫吸附测定(ELISA)检测血浆 TH 和甲状腺素载体转甲状腺素(TTR),结果表明,尽管 MMI 和 PTU 都显著降低了循环 TTR 水平(p<0.05),但只有 MMI 显著降低了血浆 TH 水平(p<0.05)。甲状腺组织的组织学分析显示,甲状腺细胞活性的改变解释了循环 TH 水平的降低。MMI 还显著上调了肝脏脱碘酶 1 和 2 的转录丰度(p<0.05),同时显著降低了垂体中 TRβ 的表达(p<0.05),这都是致甲状腺肿剂在脊椎动物 HPT 轴作用的标志。结果表明,在真鲷中,MMI 是最有效的致甲状腺肿剂,其次是 PTU,而 TU(21 天 1mg/kg 湿重)未能产生致甲状腺肿作用。该研究强调了致甲状腺肿剂对真鲷甲状腺轴的非均匀作用,并为未来研究甲状腺破坏污染物提供了基础。

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