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TAS2R bitter taste receptors regulate thyroid function
Adam A Clark1, Cedrick D Dotson2, Amanda E T Elson3
1Department of Anatomy and Neurobiology, Program in Toxicology.
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.
Insights
Type 2 taste receptors (TAS2Rs) sense bitter compounds and regulate thyroid hormone production by affecting thyroid-stimulating hormone (TSH) signaling. These findings reveal TAS2Rs as potential therapeutic targets for thyroid disorders.
Area of Science:
- Endocrinology
- Molecular Biology
- Sensory Science
Background:
- Thyroid hormones triiodothyronine (T3) and thyroxine (T4) are crucial for metabolism, development, and body composition.
- Dysregulation of T3/T4 production can lead to various health issues, necessitating the identification of novel regulatory mechanisms.
- Type 2 taste receptors (TAS2Rs), known for detecting bitter compounds, have emerged as potential regulators beyond taste perception.
Purpose of the Study:
- To investigate the role of TAS2Rs in regulating thyroid hormone production.
- To determine if TAS2Rs expressed in thyrocytes influence thyroid-stimulating hormone (TSH)-mediated signaling pathways.
- To explore the potential of TAS2Rs as therapeutic targets for thyroid dysfunction.
Main Methods:
- Immunohistochemistry and real-time PCR were used to confirm TAS2R expression in human and mouse thyrocytes and a human thyrocyte cell line (Nthy-Ori 3-1).
- Experiments involved stimulating Nthy-Ori 3-1 cells with TAS2R agonists to measure changes in intracellular calcium (Ca2+) and iodide efflux.
- A human cohort was analyzed to assess the association between TAS2R42 gene polymorphism and serum T4 levels.
Main Results:
- Human and mouse thyrocytes express multiple TAS2Rs.
- TAS2R agonists significantly reduced TSH-dependent Ca2+ increases and iodide efflux in thyrocytes in a dose-dependent manner.
- A TAS2R42 polymorphism was correlated with elevated serum T4 levels in humans, suggesting a link between TAS2Rs and thyroid hormone levels.
Conclusions:
- TAS2Rs in thyrocytes can modulate thyroid hormone production by influencing TSH signaling.
- These receptors may play a role in a protective mechanism against the ingestion of toxic substances.
- TAS2Rs represent novel druggable targets for managing hypothyroidism and hyperthyroidism.
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