Joanna Szumska

• Trace amine-associated receptor 1 (Taar1) was identified in 2001 as a receptor related to the serotonin receptor family. Taar1 was found to be expressed in thyroid and pancreas. Therefore, we designed this study in which Taar1 expression and function in the thyroid gland and pancreas of mice were analysed. The sub-cellular localization of a receptor like Taar1 determines its availability for putative ligands. Therefore, sub-cellular localization of Taar1 was analysed in thyroid tissue. Taar1 localization was confined to primary cilia. It is also noteworthy that sub-cellular localization of the Tg-processing protease, cathepsin L, was confined to primary cilia of thyrocytes. Thus, we were interested if an interaction of Taar1 with cathepsins takes place in the thyroid, and whether this affects the sub-cellular localization of Taar1. To this aim, sub-cellular localization of Taar1 was investigated in FRT cells treated with cathepsin inhibitors. Experiments revealed that Taar1 localization is altered upon inhibition of cathepsin activity. Furthermore, we determined the phenotype of the thyroid gland of taar1-/- mice in comparison to WT controls. Serum thyroid hormone concentrations were slightly decreased upon Taar1 deficiency, which was correlated with decreased expression levels and proteolytic activities of cathepsins in the thyroid gland of taar1-/- mice vs WT controls. Thereby, taar1-/- mice were characterized as mildly hypothyroid, revealing the importance of Taar1 for regulation of thyroid gland functions. Taar1 was shown previously to be also expressed in β cells of the pancreas. Thus, we aimed to investigate blood glucose concentrations upon Taar1 deficiency. However, the data showed that blood glucose levels were not affected by Taar1 deficiency. Collectively, this study revealed that Taar1 is important for various aspects of endocrine regulation in mice. Supported by Deutsche Forschungsgemeinschaft in the framework of SPP 1629, BR1308/11-1 and 11-2.