The third exoplasmic loop of the thyrotropin receptor is partially involved in signal transduction.

We characterized the role of the three exoplasmic loops in the transmembrane region of the thyrotropin receptor (TSHR) by substituting each loop with the counterpart of beta 2-adrenergic receptor amino acid sequence. Mutant El3 with a substitution of the 3rd exoplasmic loop showed significant decrease in the maximal level and sensitivity of TSH-stimulated cAMP response despite good retention of TSH binding. These findings suggest that the third exoplasmic loop of the TSH receptor is partially involved in the signal transduction mechanism.