Faculty of Pharma-Science, Teikyo University, Tokyo 173-8605, Japan.
Department of Clinical Laboratory Science, Faculty of Medical Technology, Teikyo University, Tokyo 173-8605, Japan.
Endocr J. 2022 Oct 28;69(10):1261-1269. doi: 10.1507/endocrj.EJ22-0055. Epub 2022 Jul 9.
Sulfonation is an important step in the metabolism of dopamine, estrogens, dehydroepiandrosterone, as well as thyroid hormones. However, the regulation of cytosolic sulfotransferases in the thyroid is not well understood. In a DNA microarray analysis of rat thyroid FRTL-5 cells, we found that the mRNA expression of 10 of 48 sulfotransferases was significantly altered by thyroid stimulating hormone (TSH), with that of sulfotransferase family 1A member 1 (SULT1A1) being the most significantly affected. Real-time PCR and Western blot analyses revealed that TSH, forskolin and dibutyryl cyclic AMP significantly suppressed SULT1A1 mRNA and protein levels in a time- and concentration-dependent manner. Moreover, immunofluorescence staining of FRTL-5 cells showed that SULT1A1 is localized in the perinuclear area in the absence of TSH but is spread throughout the cytoplasm with reduced fluorescence intensity in the presence of TSH. Sulfotransferase activity in FRTL-5 cells, measured using 3'-phosphoadenosine-5'-phosphosulfate as a donner and p-nitrophenol as an acceptor substrate, was significantly reduced by TSH. These findings suggest that the expression and activity of SULT1A1 are modulated by TSH in thyrocytes.
磺化是多巴胺、雌激素、脱氢表雄酮以及甲状腺激素代谢的重要步骤。然而，甲状腺中细胞溶质磺基转移酶的调节机制尚不清楚。在对大鼠甲状腺 FRTL-5 细胞的 DNA 微阵列分析中，我们发现 48 种磺基转移酶中有 10 种的 mRNA 表达受促甲状腺激素（TSH）显著改变，其中磺基转移酶家族 1A 成员 1（SULT1A1）的改变最为显著。实时 PCR 和 Western blot 分析显示，TSH、佛波酯和二丁酰环 AMP 以时间和浓度依赖的方式显著抑制 SULT1A1 mRNA 和蛋白水平。此外，FRTL-5 细胞的免疫荧光染色显示，在没有 TSH 的情况下，SULT1A1 定位于核周区，但在存在 TSH 的情况下，SULT1A1 分布于整个细胞质，荧光强度降低。用 3'-磷酸腺苷-5'-磷酸硫酸作为供体和对硝基苯酚作为受体底物测量 FRTL-5 细胞中的磺基转移酶活性，发现 TSH 显著降低了其活性。这些发现表明，TSH 可调节甲状腺细胞中 SULT1A1 的表达和活性。
