Thyrotropin binding and adenylate cyclase activation in normal and neoplastic human thyroid tissue: lack of effect of thyroglobulin.
The effects of bovine TSH (bTSH) and bovine (bTg) and human thyroglobulin (hTg) on the binding of [125I] bTSH and the activation of adenylate cyclase (AC) were studied in both normal and neoplastic human thyroid homogenates in vitro using adenylate cyclase conditions. [125I]bTSH bound specifically and with high affinity to a particulate fraction from normal thyroid and from benign and malignant thyroid neoplasms; this binding was inhibited by unlabeled bTSH (approximate Kd = 10.0 mU/ml for normal tissue; Kd = 2.5 mU/ml for thyroid neoplasms). Half-maximal activation of AC was obtained at a TSH concentration of approximately 2.5 mU/ml for both normal and neoplastic thyroid tissue, indicating that the high affinity TSH receptors are coupled to AC, at least in the neoplastic thyroid tissue. bTg and hTg did not inhibit [125I]bTSH binding to high affinity TSH receptors in either normal or neoplastic thyroid tissue. bTSH increased AC activity up to 25-fold in neoplastic thyroid tissue and up to 4-fold in normal thyroid tissue, whereas at concentrations up to 1 mg/ml, bTg had no effect. The current study demonstrates that bTSH binds to specific, high affinity receptors and stimulates AC activity in both normal and neoplastic thyroid tissue. bTg and hTg, under the conditions used in this experiment, do not influence TSH binding to its high affinity receptor in these tissues. Since Tg does not influence high affinity TSH binding or AC activity in a particulate fraction rich in plasma membranes from normal or neoplastic thyroid tissue, it is unlikely to have a modulating role on TSH action at the thyroid plasma membrane.
D000236:Adenoma / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002417:Cattle; D004789:Enzyme Activation; D006801:Humans; D013954:Thyroglobulin / Q000494:pharmacology*; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013964:Thyroid Neoplasms / Q000378:metabolism*; D013972:Thyrotropin / Q000378:metabolism*
D013972:Thyrotropin; D013954:Thyroglobulin; D000262:Adenylyl Cyclases