Effects of thyroid-stimulating hormone on adenyl cyclase activity and intermediary metabolism of "cold" thyroid...

"Cold" thyroid nodules do not concentrate (131)I before or after thyrotropin (TSH) administration. In an attempt to elucidate the reason for this TSH unresponsiveness, the effect of TSH in vitro on several metabolic parameters was studied in 11 "cold" thyroid adenomas, 2 medullary carcinomas, and in the surrounding normal thyroid tissue. Basal adenyl cyclase activity, glucose-1-(14)C oxidation, and (32)P incorporation into phospholipids were significantly greater in the adenomas than in the adjacent normal thyroid; basal cyclic 3',5'-adenosine monophosphate (cyclic AMP) concentration and adenine-(3)H incorporation into (3)H-labeled cyclic AMP were not different. In adenomas as well as normal thyroid, all parameters responded significantly to in vitro TSH stimulation. The response to TSH of adenyl cyclase activity and (32)P incorporation was enhanced in adenomas compared with that of the adjacent normal thyroid. These differences were not explained by an increased cellularity of the adenomas. Medullary carcinomas did not respond to TSH in any of the above parameters. The studies demonstrate an intact, TSH-responsive adenyl cyclase-cyclic AMP system in the adenomas and, accordingly, imply the presence of receptor sites for TSH on the cells of the adenoma. The failure of such nodules to concentrate (131)I may be owing to a subsequent impairment in the expression of cyclic AMP action on iodine metabolism.