The inhibitory effects of calmodulin antagonists on TSH-stimulated thyroid hormone release by mouse thyroid lobes.
Calcium ions have been shown to play a mojor regulatory role in the release of various hormones from a wide variety of endocrine organs. More recently, in vitro evidence suggests that a calcium-binding protein, calmodulin, is also involved in the release of many hormones. So we examined the effects of several types of calmodulin antagonists on TSH-stimulated thyroid hormone release in vitro. Mouse thyroid lobes (one thyro-tracheal unit/tube) were incubated in Krebs-Ringer bicarbonate buffer at 37 degrees C for 4h. Free thyroxine (fT4) released in the incubation medium, thyroidal cAMP and calmodulin content were measured by RIA. TSH (5 mU/ml) and dibutyryl cAMP (DBC) (200 micrograms/ml) caused a 2-4 fold increase in thyroidal release of fT4. The stimulatory effects of TSH on fT4 release were significantly inhibited by trifluoprazine and prenylamine lactate at the concentration of 5 X 10(-5) M. More specific calmodulin antagonists, W-7 and W-13, were also shown to inhibit TSH stimulation of fT4 release at the concentration of 5 X 10(-5) M. In contrast, TSH stimulation of fT4 release was not depressed by non-specific antagonists, W-5 or W-12, at the same concentration as 5 X 10(-5) M. Further, W-13 also markedly inhibited DBC-stimulated fT4 release. Neither TSH nor PGI2 altered the thyroidal calmodulin content, dissociating with a marked increase in the cAMP concentration. These results suggest that calmodulin plays an important role in TSH-stimulated thyroid hormone release and further that this mechanism exists, at least in part, at the site subsequent to the generation of cAMP.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D007773:Lactates / Q000494:pharmacology; D008297:Male; D051379:Mice; D011299:Prenylamine / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology*; D013974:Thyroxine / Q000378:metabolism*; D014268:Trifluoperazine / Q000494:pharmacology
D002147:Calmodulin; D007773:Lactates; D013449:Sulfonamides; D014268:Trifluoperazine; D003994:Bucladesine; C017967:W 7; C053347:prenylamine lactate; C033772:N-(4-aminobutyl)-5-chloro-2-naphthalenesulfonamide; D013972:Thyrotropin; D000242:Cyclic AMP; D011299:Prenylamine; D013974:Thyroxine