The contribution of subunits of thyroid stimulating hormone to the binding and biological activity of thyrotropin.
The binding of bovine TSH (thyroid stimulating hormone), LH (luteinizing hormone), and their subunits to the TSH receptor of beef thyroid membranes was compared to stimulation by these agents of adenylate cyclase [ATP pyrophosphate-lyase(cyelizing), EC 4.6.1.1] in the same membranes, glucose oxidation in dog thyroid slices, and the secretory process in mouse thyroids in vitro (colloid droplet formation) and in vivo (hormone release). The beta-subunits of TSH and LH can bind to the TSH receptor and can activate thyroid function in vitro. In contrast, the alpha-subunit of TSH binds negligibly to the TSH receptor and has very low potency for stimulation of thyroid function (except for colloid droplet formation). Neither binding nor the biological activity of the beta-subunits can be accounted for by TSH contamination, whereas this cannot be ruled out for alpha-TSH. LH binds to the TSH receptor even better than the beta-subunit of TSH but the increased binding does not result in a corresponding activation of thyroid function. Neither alpha- nor beta-TSH alone can induce more than 4-8% of the response to intact TSH in any of the investigated parameters. It is proposed that the beta-subunit has within its structure the primary determinants which are necessary to stimulate biological activity, whereas the alpha-subunit imposes conformational changes on the beta-subunit which in intact TSH promote binding and biological activity commensurately but in LH promote only binding.
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001681:Biological Assay; D002250:Carbon Radioisotopes; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D002845:Chromatography; D004285:Dogs; D005947:Glucose / Q000378:metabolism; D066298:In Vitro Techniques; D007986:Luteinizing Hormone / Q000378:metabolism; D051379:Mice; D011487:Protein Conformation; D011956:Receptors, Cell Surface; D013268:Stimulation, Chemical; D013329:Structure-Activity Relationship; D013961:Thyroid Gland / Q000378:metabolism*; D013972:Thyrotropin / Q000378:metabolism*; D014316:Tritium
D002250:Carbon Radioisotopes; D011956:Receptors, Cell Surface; D014316:Tritium; D007986:Luteinizing Hormone; D013972:Thyrotropin; D000262:Adenylyl Cyclases; D005947:Glucose