Morgado Isabel, Campinho Marco A, Costa Rita, Jacinto Rita, Power Deborah M
CCMAR, CIMAR, Laboratório Associado, University of Algarve, Campus de Gambelas, 8005-139 Faro, Portugal.
Aquat Toxicol. 2009 May 17;92(4):271-80. doi: 10.1016/j.aquatox.2009.02.015. Epub 2009 Mar 6.
Some environmental contaminants are thought to cause disruption of the thyroid system in vertebrates acting as endocrine disrupting chemicals (EDCs). Such chemicals may affect synthesis, transport and metabolism of thyroid hormones (THs). Ioxynil (IOX) and diethylstilbestrol (DES) are potential EDCs with strong affinity in vitro for sea bream transthyretin (TTR), a TH distributor protein (THDP). The aim of the present study was to establish how such chemicals influence the thyroid axis in sea bream (Sparus aurata). DES, IOX and propilthyouracil (PTU, a goitrogen) were administered in the diet to sea bream juveniles at 1 mg/kg fish (n = 14/treatment) for 21 days. After exposure plasma TH levels, quantified by RIA, were similar to those of control fish (p > 0.05) in all treatment groups. Analysis by quantitative PCR revealed that all treatments down-regulated TSH gene transcription (p < 0.05) in the brain and pituitary and deiodinase II and III transcription in the brain (p < 0.001). In contrast, PTU caused DII up-regulation in the liver (p < 0.05). Thyroid receptor beta (TRbeta) transcription was down-regulated in the pituitary by PTU (p < 0.001) and DES (p < 0.05). TTR plasma levels, quantified by ELISA, were elevated by all the chemicals including PTU (p < 0.001) which also increased TTR gene transcription in the liver (p < 0.05). Thyroid histology indicated follicular hyperstimulation in all treatments with marked hyperplasia, hypertrophy and colloid depletion in the PTU group. It appears therefore, that in vitro TTR-binders, IOX and DES, can strongly influence several components of the fish thyroid system in vivo but that the thyroid axis may have the ability to maintain or re-establish plasma TH homeostasis.
一些环境污染物被认为会扰乱脊椎动物的甲状腺系统，充当内分泌干扰化学物质（EDCs）。这类化学物质可能会影响甲状腺激素（THs）的合成、运输和代谢。碘苯腈（IOX）和己烯雌酚（DES）是潜在的EDCs，在体外对鲷鱼转甲状腺素蛋白（TTR，一种甲状腺激素转运蛋白（THDP））具有很强的亲和力。本研究的目的是确定这类化学物质如何影响鲷鱼（Sparus aurata）的甲状腺轴。将DES、IOX和丙硫氧嘧啶（PTU，一种致甲状腺肿物质）以1 mg/kg鱼的剂量添加到饲料中投喂鲷鱼幼鱼（每组n = 14），持续21天。暴露后，通过放射免疫分析（RIA）定量的血浆甲状腺激素水平在所有处理组中与对照鱼相似（p > 0.05）。定量PCR分析显示，所有处理均下调了大脑和垂体中促甲状腺激素（TSH）基因的转录（p < 0.05）以及大脑中脱碘酶II和III的转录（p < 0.001）。相反，PTU导致肝脏中脱碘酶II上调（p < 0.05）。PTU（p < 0.001）和DES（p < 0.05）使垂体中的甲状腺受体β（TRbeta）转录下调。通过酶联免疫吸附测定（ELISA）定量的TTR血浆水平在包括PTU在内的所有化学物质处理后均升高（p < 0.001），PTU还增加了肝脏中TTR基因的转录（p < 0.05）。甲状腺组织学检查表明，所有处理均出现滤泡过度刺激，PTU组有明显的增生、肥大和胶体消耗。因此，体外TTR结合剂IOX和DES似乎能在体内强烈影响鱼类甲状腺系统的多个组成部分，但甲状腺轴可能有能力维持或重新建立血浆甲状腺激素的稳态。
