Thyrotropin binding and adenylate cyclase stimulation in thyroid neoplasms.

Experiments were performed to determine whether thyroid-stimulating hormone (TSH) receptors coupled to adenylate cyclase are present in both benign and differentiated malignant thyroid tumors, and to identify abnormalities in the TSH receptor-adenylate cyclase system in neoplastic thyroid tissue. TSH binding and adenylate cyclase assays were performed under the same in vitro cyclase conditions. 125I-bovine TSH was incubated with an 8,000 X g thyroid or thyroid tumor particulate fraction from both normal and most neoplastic tissue two receptor sites were identified. The association constant for the high-affinity receptor from normal thyroid was 10.5 +/- 3.2 nM (mean +/- standard error) with a capacity of 0.8 +/- 0.3 pM/mg particulate protein. The association constant of the high-affinity receptor found in the particulate fraction from the thyroid adenomas was 3.5 +/- 0.5 nM with a capacity of 0.4 +/- 0.1 pM/mg particulate protein; for the thyroid carcinomas the association constant was 1.4 +/- 0.3 nM and the capacity 0.2 +/- 0.1 pM/mg particulate protein. The maximum adenylate cyclase response to TSH for particulate fractions from both benign and malignant tumors was greater (P less than 0.05) than in the particulate fraction from normal adjacent thyroid tissue. There was also a positive correlation between the equilibrium constants for 125I-bTSH binding and adenylate cyclase activation suggesting that binding sites are coupled to cyclase in the neoplastic tissue and that the binding observed in these experiments is of biologic consequence.