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.

Genotyping Analysis of Bitter-Taste Receptor Genes <i>TAS2R38</i> and <i>TAS2R46</i> in Japanese Patients with Gastrointestinal Cancers

“…The epithelial cells were shown to respond to PTC and also quarumsensing molecules like N-butyryl-l-homoserine lactone differentially according to the TAS2R38 genotypes so that the susceptibility to bacterial infection is maximal for AVI/AVI cells but minimal for PAV/PAV cells. Clark et al showed that human thyroid follicular cells also express TAS2R38 and other TAS2Rs and that the iodide efflux from the cells is suppressed by various bitter TAS2R ligands dose-dependently (15). Interestingly, the response was absent for a TAS2R38 agonist, PROP, in the cells derived from AVI/AVI carriers, suggesting that thyroid hormone is down-regulated by TAS2R38 and other TAS2R signaling in the thyroid follicular cells.…”

“…In humans, TAS2Rs belong to a family of 25 functional members that are clustered on chromosomes 5, 7, and 12 (1,4). TAS2Rs are expressed in various organs, including the gustatory organs, gastrointestinal tract, thyroid gland, respiratory organs, kidney, central nervous system, skin, and reproductive organs (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Many genetic polymorphisms have been identified for TAS2Rs, some of which are known to cause functional changes in bitter-taste sensitivity.…”

“…TAS2Rs are also known to be involved in non-gustatory physiology and pathology, including susceptibility to various diseases. Amish family diabetes (24), thyroid function (15), and susceptibility to respiratory infection (10) have been shown to be associated with polymorphisms in TAS2R9, TAS2R42, and TAS2R38, respectively. TAS2Rs may also be associated with cancer susceptibility.…”

Comprehensive Analysis of Mouse Bitter Taste Receptors Reveals Different Molecular Receptive Ranges for Orthologous Receptors in Mice and Humans

“…In light of findings showing that Tas2r are present in organs that are not at all or only partially accessible to xenobiotics, such as brain (86 -89), testes (61,90,91), thyroid (92), and urethra (93), we also examined whether hormones could function as Tas2r activators. We found that progesterone stimulated Tas2r114 and Tas2r110.…”

Identification of cholinergic chemosensory cells in mouse tracheal and laryngeal glandular ducts

“…urethra, thymus, thyroid gland, heart, auditory tube, airways and lung [1][2][3][4][5][6][7]. In mucosal epithelia, these chemosensory cells express one or more members of the taste receptor family 1 (Tas1R) (sweet and umami) and Tas2R (bitter) that are coupled to various G-proteins (e.g.…”