title: TAS2R bitter taste receptors regulate thyroid function.
abstract: 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 Ca(2+) 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 Ca(2+) release in Nthy-Ori 3-1 cells, but not basal Ca(2+) levels, in a dose-dependent manner. Ca(2+) 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.
authors.affiliation: Department of Anatomy and Neurobiology, Program in Toxicology.
authors.forename: Adam A
authors.initials: AA
authors.lastname: Clark
authors.affiliation: Department of Anatomy and Neurobiology.
authors.forename: Cedrick D
authors.initials: CD
authors.lastname: Dotson
authors.affiliation: Department of Anatomy and Neurobiology, Program in Neuroscience, and.
authors.forename: Amanda E T
authors.initials: AE
authors.lastname: Elson
authors.affiliation: Department of Molecular Genetics, German Institute of Human Nutrition Potsdam Rehbruecke, Nuthetal, Germany; and.
authors.forename: Anja
authors.initials: A
authors.lastname: Voigt
authors.affiliation: Department of Pharmacology and Toxicology, University of Saarland School of Medicine, Homburg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Boehm
authors.affiliation: Department of Molecular Genetics, German Institute of Human Nutrition Potsdam Rehbruecke, Nuthetal, Germany; and.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Meyerhof
authors.affiliation: Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA;
authors.forename: Nanette I
authors.initials: NI
authors.lastname: Steinle
authors.affiliation: Department of Anatomy and Neurobiology, Program in Toxicology, Program in Neuroscience, and Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland, USA; steven.munger@ufl.edu.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Munger
mesh_terms: D000328:Adult; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008024:Ligands; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D013961:Thyroid Gland / Q000166:cytology / Q000378:metabolism*; D013963:Thyroid Hormones / Q000378:metabolism; D013972:Thyrotropin / Q000378:metabolism; D014018:Tissue Distribution; D000098706:Taste Receptors, Type 2
chemical_list: D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D013963:Thyroid Hormones; D000098706:Taste Receptors, Type 2; D013972:Thyrotropin; D002118:Calcium
keywords: G protein-coupled receptor; T2R; iodide; thyrocyte; thyroxine