Thyrotropin (TSH) receptor and adenylate cyclase activity in human thyroid tumors: absence of high affinity receptor and loss of TSH responsiveness in undifferentiated thyroid carcinoma

Abstract

TSH receptor and adenylate cyclase activity of plasma membrane fractions of human thyroid tumors were examined. The mean (+/- SD) basal adenylate cyclase activity in normal thyroid tissues was 0.35 +/- 0.33 nmole/mg protein x 10 min. The activity rose to 280% (range, 270-310%) of basal with TSH (166 mU/ml). In adenomas, the activity rose to 600% (range, 530-650), which was significantly higher than that of normal thyroid (P < 0.005). In the differentiated carcinoma, TSH responsiveness of adenylate cyclase was heterogenous (range, 110-520), but was qualitatively similar to that of the normal thyroid. On the other hand, basal adenylate cyclase activity of undifferentiated carcinoma was significantly lower than that of normal thyroid (0.018 +/- 0.007 nmol/mg protein x 10 min; P < 0.05) and was not stimulated by TSH. LH, FSH, and ACTH did not stimulate the enzyme in either kind of carcinomas. The mean (+/- SD) of the capacity of the high affinity receptor of adenomas (0.72 +/- 0.64 pmol/mg protein) and differentiated carcinomas (0.77 +/- 0.84) was not significantly different from that of normal thyroid (0.92 +/- 0.84). The affinity constants of the receptors in these three tissues were much the same (1.6-2.4 x 10(10) M-1). On the other hand, high affinity receptor could not be detected in all of the undifferentiated thyroid carcinoma. It seems likely that the failure of adenylate cyclase to respond to TSH in undifferentiated carcinoma of the thyroid is due to an alteration at the level of the receptor site. These data suggest that growth and metabolic activity of undifferentiated carcinoma may be independent of TSH, while those of adenoma and differentiated carcinoma may be affected by TSH.