Thyrotropin receptor-adenylate cyclase function in human thyroid neoplasms.
The action of thyrotropin (TSH) on plasma membranes was studied to elucidate the mechanism of hormonal regulation of malignant versus normal human thyroid tissue. Thyroid plasma membranes of six specimens of papillary or follicular carcinoma and six of adenoma, as well as adjacent normal tissue obtained from these patients, were evaluated with respect to binding of 125I-labeled TSH and stimulation of adenylate cyclase. Scatchard analysis of TSH binding revealed the presence of two species of binding sites in normal thyroid of different affinities and capacities. In 11 of 12 tumors studied, the high-affinity binding site remained intact; however, the total number of low-affinity sites was markedly lower than normal tissue. Other parameters of binding were not altered in neoplastic thyroid. In each of these tissues, the hormone responsiveness and kinetics of adenylate cyclase activation were essentially identical to those observed in normal tissue, although basal activity was typically greater in the neoplasm. One carcinoma was totally deficient in both 125I-labeled TSH binding and TSH-stimulatable adenylate cyclase, although basal activity was detected. Furthermore, adenylate cyclase of this specimen was not activated by prostaglandin, in contrast to normal thyroid and other thyroid tumors. These results suggest that: (a) clinical behavior of thyroid carcinomas may not be reflected by TSH receptor-adenylate cyclase function; (b) lack of clinical response as manifest by tumor regression cannot be ascribed to the absence of functional TSH receptors or adenylate cyclase; and (c) decreased low-affinity binding present in tumors is not correlated with altered hormone responsiveness of adenylate cyclase but may reflect more general cancer-induced changes in membrane structure or composition.
D000236:Adenoma / Q000201:enzymology / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism*; D002277:Carcinoma / Q000201:enzymology / Q000378:metabolism; D002462:Cell Membrane / Q000201:enzymology; D004789:Enzyme Activation; D006160:Guanosine Triphosphate / Q000031:analogs & derivatives; D006801:Humans; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012969:Sodium Fluoride / Q000494:pharmacology; D013964:Thyroid Neoplasms / Q000201:enzymology / Q000378:metabolism*; D013972:Thyrotropin / Q000378:metabolism
D011956:Receptors, Cell Surface; D006160:Guanosine Triphosphate; D012969:Sodium Fluoride; D013972:Thyrotropin; D000262:Adenylyl Cyclases