Supplementary Material for: Differences in Mouse Hepatic Thyroid Hormone Transporter Expression with Age and Hyperthyroidism

<b><i>Background:</i></b> 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. <b><i>Objectives:</i></b> In this paper, we address possible changes in TH transporter expression in liver tissues as a mechanism of age-dependent variation in TH action. <b><i>Methods:</i></b> 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 (T<sub>4</sub>) 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. <b><i>Results:</i></b> Baseline serum free T<sub>4</sub> (fT<sub>4</sub>) concentrations were significantly higher in euthyroid young compared to old mice. T<sub>4</sub> treatment increased total T<sub>4</sub>, fT<sub>4</sub> 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 <i>Mct8</i> and <i>Oatp1a1 </i>expression levels<i>.</i> Hyperthyroidism resulted in upregulation of <i>Mct10</i>, <i>Lat1</i> and <i>Lat2</i> in liver tissue, while <i>Oatp1a1</i>, <i>Oatp1b2</i> and <i>Oatp1a4 </i>expression was downregulated. This effect was preserved in old animals. <b><i>Conclusion:</i></b> 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.

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