The thyrotropin receptor from bovine thyroid plasma membranes has been 
solubilized using lithium diiodosalicylate, and an assay to measure thyrotropin 
binding to the solubilized receptor has been developed. Both the solubilized 
thyrotropin receptor and the thyrotropin receptor on thyroid plasma membranes 
have effectively identical nonlinear Scatchard plots and negatively sloped Hill 
plots, i.e. both preparations have receptors which appear to exhibit a similar 
negatively cooperative relationship. Although the pH optimum of thyrotropin 
binding to the solubilized receptor is the same as that of the thyroid plasma 
membrane receptor, pH 6.0, the pH dependency curve of the solubilized receptor 
is slightly different in its outline. Thyrotropin binding to the solubilized 
receptor is less sensitive to salt inhibition than is binding to the thyroid 
plasma membrane receptor; however, optimal binding remains at 0 degrees. The 
relative affinities of thyrotropin and two glycoprotein hormones which can be 
considered structural analogs, luteinizing hormone and human chorionic 
gonadotropin, are 100:10:5, respectively, toward plasma membrane receptors, but 
100:25:40 toward the solubilized receptors. The solubilized receptor preparation 
is heterogeneous in size in that it has binding components with molecular 
weights of 286,000, 160,000, 75,000, and 15,000 to 30,000. Tryptic digestion 
converts all three higher molecular weight components to the 15,000 to 30,000 
molecular weight species, and the 15,000 to 30,000 molecular weight receptor 
component has all of the binding properties of the solubilized receptor 
preparation before tryptic digestion including an identical nonlinear Scatchard 
plot. It has the same size as and coelutes from Sephadex G-100 with a 15,000 to 
30,000 molecular weight receptor released by tryptic digestion of bovine thyroid 
plasma membranes or tryptic digestion of bovine or dog thyroid cells in culture. 
The tryptic fragment of the solubilized receptor or preparations has been 
purified almost 250-fold by affinity chromatography on thyrotropin-Sepharose 
columns. The binding activity is lost when the solubilized thyrotropin receptor 
preparation is exposed to beads of neuraminidase-Sepharose or conconavalin 
A-Sepharose.