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

## TL;DR

Steroid hormones can activate human bitter taste receptors, suggesting they may have important physiological roles beyond taste.

## Contribution

The study identifies steroid hormones as potent and putatively endogenous activators of TAS2R14 and TAS2R46 bitter taste receptors.

## Key findings

- TAS2R46 was found to be more sensitive to steroid hormones than TAS2R14.
- Some steroid hormones activated TAS2R46 with extraordinarily high potencies.
- Steroid hormone levels in the body can reach concentrations that activate TAS2Rs.

## Abstract

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.

Human bitter taste receptors are not only involved in sensing tastants within the oral cavity but also play crucial roles in internal tissues of the body. The current report identifies numerous structurally and functionally diverse steroid hormones as activators of the two human bitter taste receptors, TAS2R14 and TAS2R46. As endogenous agonists of bitter taste receptors, steroid hormones could play important physiological roles. [Image created in BioRender. https://BioRender.com/985s9cz]