• Bitter Taste Receptor Expression and Function in the Thyroid

      Clark, Adam Austin; Munger, Steven D. (2014)
      The environment is filled with beneficial and harmful compounds. The gustatory system provides a tool to screen them, guiding intake and avoidance. Five human taste perceptions-sweet, sour, bitter, salty, and umami-provide information for this task. For example, compounds perceived as sweet tasting are highly appetitive, and identify energy rich simple sugars like glucose. Alternatively compounds eliciting the perception of bitterness, an adverse sensation, identify structural motifs associated with toxins. These characteristics outline how taste perceptions help determine the biological impact of the substances in our surroundings. Recent discoveries of taste receptor expression in extraoral tissues, further supports the importance of these receptors. Extraoral taste receptors propagate non-taste associated responses. For example, sweet taste receptors located in entero-endocrine cells of the gut signal for proper utilization of energy rich sugars. By contrast, bitter taste receptors in the upper and lower airways detect irritants and initiate actions helpful in eliminating or reducing pathogens or toxins. Expression of extraoral bitter taste receptors (T2Rs) and their role in recognition and response to toxins has formed the basis of my research, with my thesis focusing on characterization of T2Rs in the human thyroid. My research findings are subdivided into three studies. The first characterized expression of T2Rs in the thyroid using molecular biological analysis and immunohistochemical techniques, which identified mRNA and protein expression of thyroid T2Rs and the taste associated G protein subunit α-gustducin. The second study identified a functional role of thyroid T2Rs utilizing Ca2+ and iodide signaling assays. Stimulation of thyroid cells with various levels of thyroid stimulating hormone (TSH) with or without T2R agonists indicates that bitter-tasting stimuli inhibit TSH-mediated Ca2+ signaling and iodide efflux. The third study aimed to test the effects of T2R agonists on thyroid hormone production in vivo, by assessing changes in mouse thyroxine levels after exposure to T2R agonists. My findings implicate thyroid T2Rs in the regulation of TSH signaling in thyrocytes and suggest that these receptors in turn modulate thyroid hormone production. T2R-mediated thyroid hormone modulation may serve as a protective response to toxin ingestion.