In Vitro and In Vivo Refractoriness to Thyrotropin Stimulation of Iodine Organification and Thyroid Hormone Secretion

TLDR: TSH-induced refractoriness also includes effects on organification of iodine and secretion of thyroid hormone and effects of dibutyryl cyclic AMP and prostagladin E(1) were also inhibited by prior exposure to TSH.

Abstract: A B S T RA C T Earlier studies indicated that initial exposure of thyroid slices to thyrotropin diminished responsiveness of the adenylate cyclase-cyclic AMP system, glucose oxidation, and 32Pi incorporation into phospholipids upon readdition of the hormone. The present studies demonstrate that slices from dog, beef, and human thyroid glands initially incubated with thyrotropin (TSH) were less responsive to subsequent addition of the hormone when organification of iodide was examined. Increasing the amount of TSH did not overcome the refractoriness induced by the initial exposure to the hormone. Furthermore, the stimulatory effects of dibutyryl cyclic AMP and prostagladin E1 were abolished in slices previously incubated with TSH. Development of such refractoriness did not depend upon new protein synthesis and was not abolished by 1 mM prophylthiouracil in the first incubation. Addition of 0.1 ,uM thyroxine or triiodothyronine or 1.5 ,M iodide during all three incubations did not modify the response to TSH, added for the first time in the third incubation. However, 1mM iodide in the buffer during all three incubations inhibited the response toTSH during the third incubation. During the refractory period, effects ofTSH on colloid droplet formation were also diminished. The in vivo effect ofTSH on serum 1- triiodothyronine in rats was significantly reduced when the rats had been injected with TSH 8 h earlier. These studies demonstrate that TSH-induced refractoriness also includes effects on organification of iodine and secretion of thyroid hormone. The results cannot be adequately explained by