TAS2R bitter taste receptors regulate thyroid function

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.—Clark, A. A., Dotson, C. D., Elson, A. E. T., Voigt, A., Boehm, U., Meyerhof, W., Steinle, N. I., Munger, S. D., TAS2R bitter taste receptors regulate thyroid function. FASEB J. 29, 164–172 (2015). www.fasebj.org