Modulation of thyroglobulin release by dog thyroid slices.
Nonbutanol-extractable 131I (NBE131I) release by dog thyroid slices in vitro has been shown previously to be primarily thyroglobulin (Tg); it is stimulated by TSH. NBE131I (Tg) release has therefore been considered as an in vitro model of thyroglobulin secretion and was further characterized in this work. TSH-stimulated NBE131I (Tg) release, like TSH-stimulated BE131I (T4, T3 and iodide) release was reproduced by forskolin, an activator of adenylate cyclase. TSH-, (Bu)2cAMP- and forskolin-stimulated NBE131I (Tg) release was inhibited by 10(-5) M carbamylcholine, an effect relieved by 10(-5) M atropine, but not by 10(-4) M 1-methyl-3-isobutylxanthine. NBE131I (Tg) release was observed in the presence of 2 mM methimazole and 2 mM perchlorate. Cooling the slices to 20 degrees C or addition of 10(-5) M monensin completely blocked the formation of apical pseudopods and BE131I release but not NBE131I (Tg) release. Inhibition by 500 microM chloroquine of intralysosomal Tg hydrolysis and BE131I release did not enhance NBE131I (Tg) release. Cytochalasin B induced a concentration-dependent increase in basal and TSH-stimulated NBE131I (Tg) release at concentrations which depressed TSH-stimulated BE131I release. Removal of Ca2+ from the medium and slices by 10(-3) M or 10(-4) M EGTA increased NBE131I (Tg) release. In conclusion, in dog thyroid slices, TSH-stimulated NBE131I (Tg) release was mediated by cAMP and inhibited by 10(-5) M carbamylcholine at a step beyond cAMP. It was not neosynthesized Tg. It did not seem to require the formation of apical pseudopods or to result from the escape from lysosomes of undegraded thyroglobulin.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D003078:Colchicine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D004285:Dogs; D000431:Ethanol / Q000494:pharmacology; D066298:In Vitro Techniques; D007700:Kinetics; D008985:Monensin / Q000494:pharmacology; D009550:Nigericin / Q000494:pharmacology; D013954:Thyroglobulin / Q000378:metabolism*; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology
D005576:Colforsin; D003571:Cytochalasin B; D000431:Ethanol; D003994:Bucladesine; D013972:Thyrotropin; D013954:Thyroglobulin; D008985:Monensin; D009550:Nigericin; D003078:Colchicine