Effect of thyrotropin-induced desensitization of bovine thyroid adenylate cyclase on the nucleotide regulatory protein.
The stimulation of adenylate cyclase by TSH was decreased 50-60% in crude membranes prepared from homogenates of bovine thyroid slices that had previously been incubated for 2 h with the hormone. The diminished response was not associated with any significant change in the binding capacity or affinity for 125I-labeled TSH. The apparent affinities of the desensitized adenylate cyclase for TSH or GTP were not different from those of the enzyme prepared from thyroid slices that had been incubated without TSH. Decreased adenylate cyclase responses to NaF, cholera toxin, or guanyl-5'-yl-imidodiphosphate were also observed in the desensitized membrane, whereas the enzyme responses to prostaglandin E1, GTP, or forskolin were not decreased. However, desensitization caused no decrease in the cholera toxin-catalyzed ADP ribosylation of the 40,000 mol wt polypeptide guanine nucleotide-binding component of the adenylate cyclase. The desensitized membranes showed basal adenylate cyclase activity similar to that of the control membranes using adenyl-5'-yl-imidodiphosphate as substrate in the absence of a nucleotide-regenerating system. These results suggest that the in vitro TSH-induced desensitization of thyroid adenylate cyclase reflects an alteration in the activation processes of the nucleotide regulatory protein.
D000246:Adenosine Diphosphate Ribose / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000266:Adenylyl Imidodiphosphate / Q000378:metabolism; D000527:Alprostadil; D000818:Animals; D002417:Cattle; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin; D004224:Diterpenes / Q000494:pharmacology; D004361:Drug Tolerance; D006160:Guanosine Triphosphate / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D013961:Thyroid Gland / Q000201:enzymology*; D013972:Thyrotropin / Q000378:metabolism / Q000494:pharmacology*
D004224:Diterpenes; D011458:Prostaglandins E; D005576:Colforsin; D000246:Adenosine Diphosphate Ribose; D000266:Adenylyl Imidodiphosphate; D006160:Guanosine Triphosphate; D013972:Thyrotropin; D002772:Cholera Toxin; D000262:Adenylyl Cyclases; D000527:Alprostadil