Thyrotropin-receptor interaction and cyclic AMP-mediated effects in thyroid cells.
Thyroid cells in culture constitute a suitable system for the study of thyroid gland function and its regulation. The natural thyroid stimulator (TSH) induces the in vitro reorganization of thyroid cells into three-dimensional follicles morphologically and metabolically similar to gland follicles. In contrast, nonstimulated cells develop as a monolayer and in a concerted manner rapidly lose the enzymes involved in iodine metabolosm and the aptitude to bind TSH to specific receptor sites. The morphogenetic action of TSH and its ability to maintain the specific metabolic properties of thyroid cells in culture are mediated by cyclic AMP via new RNA and new protein synthesis. Therefore comparison of the properties of a given cell type in morphologically and metabolically different status should provide a valuable tool for studying the TSH mechanism of action. Using 125-I-labeled TSH of high purity, high specific radioactivity, and preserved biologic potency, TSH interaction with intact cells and their derived plasma membranes was studied. At both the cellular and the sub-cellular level a very good agreement was found for the values of the rate and equilibrium constants of labeled TSH binding. A single type of high-affinity low-capacity site was revealed. In contrast, in both systems dissociation of bound labeled TSH was not of single-order kinetics and showed two kinetic components with half-lives of 3 and 30 min. An excellent correlation between half-stimulation of adenylate cyclase and iodide transport mechanism activation, and the dissociation constant of TSH binding, was found, indicating that the in vitro system studied was relevant to physiologic regulation.
D000818:Animals; D001665:Binding Sites; D003994:Bucladesine / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000494:pharmacology*; D007700:Kinetics; D008433:Mathematics; D008854:Microscopy, Electron; D011956:Receptors, Cell Surface; D013552:Swine; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D013972:Thyrotropin / Q000378:metabolism*; D013997:Time Factors
D011956:Receptors, Cell Surface; D003994:Bucladesine; D013972:Thyrotropin; D000242:Cyclic AMP