Effect of thyroid statuses on sodium/iodide symporter (NIS) gene expression in the extrathyroidal tissues in mice

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Abstract
Background: Iodide that is essential for thyroid hormone synthesis is actively transported into the thyroid follicular cells via sodium/iodide symporter (NIS) protein in vertebrates. It is well known that NIS expression in thyroid is regulated by the thyroid statuses mainly through thyroid stimulating hormone (TSH). AlthoughNISmRNA expressions in extrathyroidal tissues have been qualitatively reported, their regulation by thyroid statuses has not been well clarified.Methods: Male ICR mice aged four weeks were assigned into three groups (control, hypothyroid, and hyperthyroid). Hypothyroid group of mice were treated with 0.02% methimazole in drinking water and hyperthyroid group of mice received intraperitoneal injection (4 μgL-T4twice a week) for four weeks.NISmRNA expression levels in the tissues were evaluated using Northern blot hybridization and quantitative real-time RTPCR (qPCR). Additionally, end-point RTPCR for the thyroid follicular cell-characteristic genes (TSH receptor,TSHR; thyroid transcription factor-1,TTF1; and paired box gene 8,Pax8) was carried out.Results: By Northern blot analysis,NISmRNA was detected in thyroid and stomach. In addition to these organs, qPCR revealed the expression also in the submandibular gland, colon, testis, and lung. Expression ofNISmRNA in thyroid was significantly increased in hypothyroid and decreased in hyperthyroid group. Trends ofNISmRNA expression in extrathyroidal tissues were not in line with that in the thyroid gland in different thyroid statuses. Only in lung,NISmRNA was regulated by thyroid statuses but in opposite way compared to the manner in the thyroid gland. There were no extrathyroidal tissues that expressed all three characteristic genes of thyroid follicular cells.Conclusions: NISmRNA expression in the thyroid gland was up-regulated in hypothyroid mice and was down-regulated in hyperthyroid mice, suggesting thatNISmRNA in the thyroid gland is regulated by thyroid statuses. In contrast,NISmRNA expression in extrathyroidal tissues was not altered by thyroid statuses although it was widely expressed. Lack of responsiveness ofNISmRNA expressions in extrathyroidal tissues reemphasizes additional functions of NIS protein in extrathyroidal tissues other than iodide trapping.

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