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Tissue distribution and thyroid hormone effects on mRNA abundance for membrane transporters Mct8 Mct10 and organic anion-transporting polypeptides (Oatps) in a teleost fish

机译:硬骨鱼中膜转运蛋白Mct8Mct10和有机阴离子转运多肽(Oatps)的组织分布和甲状腺激素对mRNA丰度的影响

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摘要

Many of the actions of thyroid hormones (THs) occur via TH binding to intracellular receptors. Although it was long thought that THs diffused passively across plasma membranes, it is now recognized that cellular entry is mediated by a variety of membrane transporter proteins. In this study, we identified cDNAs encoding the TH transporters monocarboxylate transferase 8 (mct8) and 10 (mct10) as well as eight distinct organic anion-transporting polypeptide (oatp) proteins from fathead minnow (Pimephales promelas). Analysis of the tissue distribution of transporter mRNAs revealed that mct8 and mct10 transcripts were both abundant in liver, but also present at lower levels in brain, gonad and other tissues. Transcripts encoding oatp1c1 were highly abundant in brain, liver and gonad, and exhibited significant sex differences in the liver and gonad. Treatment of adult male minnows with 3,5,3′-triiodothyronine (T3) or the goitrogen methimazole altered gene transcript abundance for several transporters. Fish given exogenous T3 had reduced mct8 and oapt1c1 mRNA levels in the liver compared to methimazole-treated fish. In the brain, transcripts for mct8, mct10, oatp2b1, and oatp3a1 were each reduced in abundance in fish with elevated T3. As a whole, these results provide evidence that TH status influences the transcriptional dynamics of mct8, mct10 and several Oatp genes including oatp1c1 in teleost fish.
机译:甲状腺激素(THs)的许多作用是通过TH与细胞内受体结合而发生的。尽管长期以来人们一直认为TH会在质膜上被动扩散,但现在人们认识到,细胞进入是由多种膜转运蛋白介导的。在这项研究中,我们确定了编码TH转运蛋白单羧酸转移酶8(mct8)和10(mct10)的cDNA,以及来自黑头fat(Pimephales promelas)的八个不同的有机阴离子转运多肽(oatp)蛋白。对转运蛋白mRNA的组织分布的分析显示,肝脏中的mct8和mct10转录本都丰富,但在脑,性腺和其他组织中的含量却较低。编码oatp1c1的转录本在脑,肝和性腺中高度丰富,并且在肝和性腺中表现出明显的性别差异。用3,5,3'-三碘甲腺氨酸(T3)或goitrogen甲硫咪唑治疗成年雄性min鱼改变了几种转运蛋白的基因转录本丰度。与甲巯咪唑处理的鱼相比,给予外源性T3的鱼肝脏中的mct8和oapt1c1 mRNA水平降低。在大脑中,T3升高的鱼的mct8,mct10,oatp2b1和oatp3a1的转录本各自都减少了。总体而言,这些结果提供了TH状态影响硬骨鱼中mct8,mct10和包括Oatp1c1在内的多个Oatp基因的转录动力学的证据。

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