Steroid Hormones Are Potent and Putatively Endogenous Activators of Human Bitter Taste Receptors

Human bitter taste plays an important role in the quality assessment of food. The presence of the corresponding receptors, the taste receptor 2 family (TAS2Rs), in nongustatory tissues without direct contact to the environment suggested that, apart from food compounds, putative endogenous agonists may also exist. Recent studies on bitter taste receptors of vertebrates, including humans, identified occasional steroid hormones as agonists for these receptors; therefore, steroid hormones represent relevant, potentially endogenous agonists for TAS2Rs. In this study, a comprehensive analysis of 19 steroid hormones, cholesterol, and two plant-derived hormones was performed using functional assays to assess the activation of TAS2Rs. Two TAS2Rs, TAS2R14 and TAS2R46, were found to be differentially activated by the test compounds, with TAS2R46 being in almost all cases the more sensitive receptor. Some steroid hormones activated TAS2R46 with extraordinarily high potencies. Comparison with a human metabolite database revealed that several steroid hormone levels reach activating concentrations for TAS2Rs, suggesting that TAS2Rs indeed could act as sensors for circulating steroid hormones.