[Structure-function relations of glycoprotein hormone receptors and their medical applications].

The Thyrotropin receptor (TSHr), like the other members of glycoprotein hormone receptors (GPHR) family (LH/CG and FSH receptors), presents a bipartite structure, with a carboxyl-terminal serpentine region implicated in the transmission of the signal activation and a large extracellular domain (ECD) responsible of the hormone binding with a high affinity. This asks the question of the mechanism implicated in the intra-molecular transduction of the activating signal. The GPHR can be activated by a large diversity of mutations affecting also the ectodomain. Moreover, the TSH receptor can also be activated by autoantibodies from patients with Graves' disease, responsible for hyperthyroidism. The mechanisms implicated into the stimulation by the hormone binding, "gain of function" mutations or by autoantibody from patients with Graves' disease remain unknown. Our study is mainly focusing on the knowledge of these mechanisms of activation.