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Thyroxine replacement modifies changes in deiodinase and thyroid hormone transporter expression induced by subclinical hypothyroidism in rats
Hormones ( IF 2.4 ) Pub Date : 2020-09-29 , DOI: 10.1007/s42000-020-00247-1
Kelen Carneiro Oliveira 1 , Roberto Laureano-Melo 2 , Rodrigo Rodrigues da Conceição 1 , Janaina Sena de Souza 1 , Wellington da Silva Cortês 2 , Mônica Akemi Sato 3 , Maria Izabel Chiamolera 1 , Rui Monteiro Maciel 1 , Gisele Giannocco 1, 4
Affiliation  

Purpose

The potential benefits of treating subclinical hypothyroidism (SCH) are unclear and still controversial. Thus, we surgically induced SCH in rats and evaluated the effects of thyroxine (T4) replacement on the gene expression levels of deiodinases and thyroid hormone (TH) transporters in different tissues.

Methods

SCH was induced by hemithyroid electrocauterization. The control animals underwent the same surgical procedure but were not subjected to electrocauterization (sham). After 14 days, half of the SCH animals were treated with T4 (SCH + T4). At the end of the experimental protocol, all of the rats were euthanized, serum hormone concentrations were measured, and RNA analyses were performed on different tissues and organs.

Results

Consistent with previous studies, we observed increased TSH levels, normal TH levels, and reduced hypothalamic TRH expression in the SCH group. Additionally, Dio2 mRNA expression was downregulated in the hippocampus and pituitary, and Dio1 was upregulated in the kidney and pituitary of the SCH animals. The changes in Dio3 expression were tissue-specific. Concerning TH transporters, Mct10 expression was upregulated in the pituitary, kidney, hypothalamus, and hippocampus, and Mct8 expression was downregulated in the kidney of the SCH group. Crym expression was upregulated in the kidney and pituitary. Notably, T4 replacement significantly attenuated serum TSH levels and reverted Dio1, Dio2, Mct10, and Crym expression in the pituitary, hippocampus, and kidney to levels that were similar to the sham group. Tissue-specific responses were also observed in the liver and hypothalamus.

Conclusion

Our results indicate that treatment of SCH should be considered before the appearance of clinical symptoms of hypothyroidism.



中文翻译:


甲状腺素替代改变大鼠亚临床甲状腺功能减退症引起的脱碘酶和甲状腺激素转运蛋白表达的变化


 目的


治疗亚临床甲状腺功能减退症 (SCH) 的潜在益处尚不清楚,且仍有争议。因此,我们通过手术诱导大鼠 SCH,并评估甲状腺素 (T 4 ) 替代对不同组织中脱碘酶和甲状腺激素 (TH) 转运蛋白基因表达水平的影响。

 方法


SCH是通过半甲状腺电灼诱发的。对照动物接受相同的手术程序,但不进行电灼(假手术)。 14天后,一半的SCH动物接受T 4 (SCH + T 4 )治疗。实验方案结束时,对所有大鼠实施安乐死,测量血清激素浓度,并对不同组织和器官进行RNA分析。

 结果


与之前的研究一致,我们观察到 SCH 组中 TSH 水平升高,TH 水平正常,下丘脑 TRH 表达降低。此外,SCH 动物的海马和垂体中 Dio2 mRNA 表达下调,而肾脏和垂体中 Dio1 表达上调。 Dio3 表达的变化是组织特异性的。关于TH转运蛋白,SCH组的垂体、肾脏、下丘脑和海马中Mct10表达上调,肾脏中Mct8表达下调。 Crym 表达在肾脏和垂体中上调。值得注意的是,T 4替代显着降低了血清 TSH 水平,并将垂体、海马和肾脏中的 Dio1、Dio2、Mct10 和 Crym 表达恢复到与假手术组相似的水平。在肝脏和下丘脑中也观察到了组织特异性反应。

 结论


我们的结果表明,在出现甲状腺功能减退症临床症状之前,应考虑治疗 SCH。

更新日期:2020-09-30
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