IRIBHM, ULB, Brussels, Belgium.
The thyrotropin receptor (TSHr) is a glycoprotein hormone receptor controlling the thyroid growth and the thyroid hormones production, upon stimulation by its natural ligand, the thyrotropin hormone (TSH). In some pathological situations, this receptor is activated in the absence of TSH, either by autoantibodies from patients with Graves disease (an autoimmune thyroid disease where the TSHr is targeted and activated by autoantibodies), or by activating mutations (as observed in autonomous thyroid adenomas), or by abnormally high levels of another glycoprotein hormone, the chorionic gonadotropin (hCG), produced by the placenta during the pregnancy (which results in gestational hyperthyroidism).
So far the mechanism of activation of this receptor by the TSH, autoantibodies, hCG or natural mutations remains poorly understood.
We propose here a model of activation for the TSHr which takes into account all these physiological and pathological observations.