Dissociation in the response of the adenylate cyclase system to thyrotropin and prostaglandin E2 in human thyroid carcinoma tissue.

Because the existence of a damaged thyrotropin (TSH) receptor in thyroid tumors may be relevant in the perspective of a correct postsurgical therapy, the effect of TSH on cAMP intracellular accumulation in thyroid carcinoma (N = 16), follicular adenoma (N = 27) and normal tissue (N = 30) slices was studied and compared with that of nonspecific stimulus of thyroid adenylate cyclase-cAMP system, such as prostaglandin E2 (PGE2). While in all follicular adenomas a normal behavior of basal and post-TSH and -PGE2 stimulated cAMP accumulation was observed, basal cAMP levels were generally higher than in controls in 14 differentiated carcinomas, responses to TSH were reduced or absent, and response to PGE2 was close to normal. On the contrary, in two anaplastic carcinomas, both TSH and PGE2 produced a negligible modification of cAMP levels. Thus, in undifferentiated carcinomas, the adenylate cyclase-cAMP system seems to be altered; in differentiated carcinomas, the catalytic part of the system appears unaffected as it is PGE2-responsive. Therefore, some hypotheses are ruled out as an explanation for decreased sensitivity to TSH of differentiated carcinomatous cells.