Glucose dependence of thyrotropin-stimulated thyroid hormone formation

TSH (100 mU/ml) stimulation of organic binding of iodide, including formation of T4, in bovine thyroid slices was 3-fold greater when the incubation medium contained glucose; this effect of glucose was apparent at 0.1 mM and was maximal at 1 mM. TSH at 5 mU/ml enhanced organification of iodide in calf thyroid slices only with the presence of glucose in the medium. These effects of glucose are not mediated by mechanisms involving iodide transport. TSH stimulation of O2 consumption of slices was also significantly greater in glucose-enriched medium. Glucose was also required for maximal increase of iodide organification in response to dibutyryl cAMP and prostaglandin E1 in canine thyroid slices. Glucose did not affect the TSH-stimulated increase in the cAMP content of calf thyroid slices. Galactose, fructose, or pyruvate could replace glucose in supporting TSH stimulation of organic binding; TSH increased oxidation of [1-14C]galactose, [U-14C]fructose, or [3-14C]pyruvate, as well as that of [1-14C]glucose. In thyroid slices, TSH enhanced the oxidation of formate, a process believed to be mediated by endogenous H2O2, only in glucose-supplemented medium. The addition of of H2O2 or a H2O2-generating system (tyramine) to the medium greatly increased the organic binding of iodide in thyroid slices; this stimulation, however, did not require glucose. Since both TSH- and cAMP-dependent thyroid hormone formation and H2O2 production were augmented by glucose, while glucose supplements had no effect on hormone formation in the presence of exogenous H2O2, it is concluded that the mechanism whereby glucose potentiates the observed responses to TSH involves enhanced intrathyroidal generation of H2O2.