TAS2R bitter taste receptors regulate thyroid function
TAS2R bitter taste receptors regulate thyroid function
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DOI：
10.1096/fj.14-262246
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发表时间：
2015-01-01
期刊：
影响因子：
4.8
通讯作者：
Munger, Steven D.
中科院分区：
文献类型：
--
作者：
Clark, Adam A.;Dotson, Cedrick D.;Munger, Steven D.
甲状腺激素三碘甲状腺原氨酸和甲状腺素（T3/T4）的失调会影响新陈代谢，身体成分和发育。因此，确定影响T3/T4产生的新机制至关重要。我们发现，2型味觉受体（TAS 2 Rs），这是激活的味觉化合物，如那些发现在许多食品和药品，负调节促甲状腺激素（TSH）依赖性钙离子增加和TSH依赖性碘流出甲状腺细胞。免疫组织化学Tas 2 R依赖的报告基因表达和实时PCR分析表明，人类和小鼠甲状腺细胞和Nthy-Ori 3-1人类甲状腺细胞系表达几种TAS 2 R。甲状腺细胞表达的TAS 2 R的五种不同激动剂以剂量依赖性方式降低Nthy-Ori 3-1细胞中TSH依赖性Ca 2+释放，但不降低基础Ca 2+水平。Ca 2+反应不受6-n-丙基硫氧嘧啶的影响，与其同源受体TAS 2 R38的无反应变体在这些细胞中的表达一致。TAS 2 R激动剂也抑制基础和TSH依赖性碘流出。此外，常见的TAS 2 R42多态性与人类队列中血清T4水平升高相关。我们的研究结果表明，TAS 2 Rs将检测到的有苦味的化合物与甲状腺细胞功能和T3/T4产生的变化结合起来。因此，TAS 2 Rs可能介导对过量摄入有毒物质的保护性反应，并可作为甲状腺功能减退或甲状腺功能亢进治疗的新药物靶点。
Dysregulation of thyroid hormones triiodothyronine and thyroxine (T3/T4) can impact metabolism, body composition, and development. Thus, it is critical to identify novel mechanisms that impact T3/T4 production. We found that type 2 taste receptors (TAS2Rs), which are activated by bitter-tasting compounds such as those found in many foods and pharmaceuticals, negatively regulate thyroid-stimulating hormone (TSH)-dependent Ca2+ increases and TSH-dependent iodide efflux in thyrocytes. Immunohistochemical Tas2r-dependent reporter expression and real-time PCR analyses reveal that human and mouse thyrocytes and the Nthy-Ori 3-1 human thyrocyte line express several TAS2Rs. Five different agonists for thyrocyte-expressed TAS2Rs reduced TSH-dependent Ca2+ release in Nthy-Ori 3-1 cells, but not basal Ca2+ levels, in a dose-dependent manner. Ca2+ responses were unaffected by 6-n-propylthiouracil, consistent with the expression of an unresponsive variant of its cognate receptor, TAS2R38, in these cells. TAS2R agonists also inhibited basal and TSH-dependent iodide efflux. Furthermore, a common TAS2R42 polymorphism is associated with increased serum T4 levels in a human cohort. Our findings indicate that TAS2Rs couple the detection of bitter-tasting compounds to changes in thyrocyte function and T3/T4 production. Thus, TAS2Rs may mediate a protective response to overingestion of toxic materials and could serve as new druggable targets for therapeutic treatment of hypo-or hyperthyroidism.