MUTATIONS OF THYROTROPIN RECEPTOR ISOLATED FROM THYROID AUTONOMOUS FUNCTIONING ADENOMAS CONFER TSH-INDEPENDENT GROWTH TO THYROID-CELLS

TSH receptor mutants in the VI transmembrane segment, found in thyroid autonomously functioning adeonomas, have been expressed in differenti ated thyroid cells, All mutant receptors constitutively stimulated ade nylyl cyclase, The biological activity, measured as cAMP production re lative to the wild type receptor, was specific for each mutant in tran sient and stable transfection assays. Cells expressing these mutants p roliferated in the absence of TSH, The rate of growth in the absence o f TSH paralleled basal cAMP production for each mutant receptor, Low T SH concentrations stimulated of mutant receptor-expressing growth of t he cells expressing the wild type receptor, Also, the entry in the cel l cycle and the plating efficiency were markedly stimulated by the exp ression of the mutant receptors, These data provide a molecular link b etween the occurrence of TSH receptor mutations and thyroid autonomous ly functioning adenomas.