Engels Kathrin, Rakov Helena, Zwanziger Denise, Moeller Lars C, Homuth Georg, Köhrle Josef, Brix Klaudia, Führer Dagmar
Department of Endocrinology and Metabolism, University Hospital Essen, Essen, Germany.
Department of Functional Genomics, Ernst-Moritz-Arndt University Greifswald, Greifswald, Germany.
Eur Thyroid J. 2015 Sep;4(Suppl 1):81-6. doi: 10.1159/000381020. Epub 2015 May 27.
Clinical features of thyroid dysfunction vary with age, and an oligosymptomatic presentation of hyperthyroidism is frequently observed in the elderly. This suggests age modulation of thyroid hormone (TH) action, which may occur, for example, by alterations in TH production, metabolism and/or TH action in target organs.
In this paper, we address possible changes in TH transporter expression in liver tissues as a mechanism of age-dependent variation in TH action.
Chronic hyperthyroidism was induced in 4- and 20-month-old C57BL6/NTac male mice (n = 8-10) by intraperitoneal injections of 1 µg/g body weight L-thyroxine (T4) every 48 h over 7 weeks. Control animals were injected with PBS. Total RNA was isolated from liver samples for analysis of the TH transporter and TH-responsive gene expression. TH concentrations were determined in mice sera.
Baseline serum free T4 (fT4) concentrations were significantly higher in euthyroid young compared to old mice. T4 treatment increased total T4, fT4 and free triiodothyronine to comparable concentrations in young and old mice. In the euthyroid state, TH transporter expression was significantly higher in old than in young mice, except for Mct8 and Oatp1a1 expression levels. Hyperthyroidism resulted in upregulation of Mct10, Lat1 and Lat2 in liver tissue, while Oatp1a1, Oatp1b2 and Oatp1a4 expression was downregulated. This effect was preserved in old animals.
Here, we show age-dependent differences in TH transporter mRNA expression in the euthyroid and hyperthyroid state of mice focusing on the liver as a classical TH target organ.
甲状腺功能障碍的临床特征随年龄而异，老年人中甲状腺功能亢进的症状往往较少。这表明甲状腺激素（TH）作用存在年龄调节，例如可能通过TH产生、代谢和/或靶器官中TH作用的改变而发生。
在本文中，我们探讨肝脏组织中TH转运蛋白表达的可能变化，作为TH作用年龄依赖性变化的一种机制。
通过每48小时腹腔注射1μg/g体重的L-甲状腺素（T4），持续7周，诱导4月龄和20月龄的C57BL6/NTac雄性小鼠（n = 8 - 10）发生慢性甲状腺功能亢进。对照动物注射磷酸盐缓冲液（PBS）。从肝脏样本中分离总RNA，用于分析TH转运蛋白和TH反应性基因的表达。测定小鼠血清中的TH浓度。
与老年小鼠相比，甲状腺功能正常的年轻小鼠基线血清游离T4（fT4）浓度显著更高。T4治疗使年轻和老年小鼠的总T4、fT4和游离三碘甲状腺原氨酸升高至相当的浓度。在甲状腺功能正常状态下，除Mct8和Oatp1a1表达水平外，老年小鼠的TH转运蛋白表达显著高于年轻小鼠。甲状腺功能亢进导致肝脏组织中Mct10、Lat1和Lat2上调，而Oatp1a1、Oatp1b2和Oatp1a4表达下调。这种效应在老年动物中仍然存在。
在此，我们展示了以肝脏作为经典TH靶器官，在小鼠甲状腺功能正常和亢进状态下TH转运蛋白mRNA表达存在年龄依赖性差异。
