Hydrogen peroxide inhibits iodide uptake and iodine organification in cultured porcine thyroid follicles.
We investigated the effect of hydrogen peroxide on the process of thyroid hormone formation in a physiologic culture system of porcine thyroid follicles that we recently established. Porcine thyroid follicles cultured in medium containing 1 mU/mL TSH were exposed to 0 to 500 microM hydrogen peroxide in the presence of 0.1 microCi carrier-free Na125 and sodium iodide for 2 h. Iodide uptake and iodine organification were measured in this incubation system. The kinetics of iodide uptake were used to explain the action of hydrogen peroxide. In addition, cAMP content and Na+,K(+)-ATPase activity (an enzyme necessary for iodide uptake) were measured to investigate the mechanism of hydrogen peroxide action. Hydrogen peroxide at concentrations of 100, 200, and 500 microM inhibited iodide uptake in a dose-dependent manner. Iodide organification was inhibited only when the concentration of hydrogen peroxide was greater than 200 microM. The kinetics of iodide uptake indicated that hydrogen peroxide was a noncompetitive inhibitor with iodide. Inhibition of iodide uptake and iodine organification by hydrogen peroxide were not mediated by alteration of cAMP content of Na+,K(+)-ATPase activity, since exposure to even 500 microM hydrogen peroxide did not change these parameters in the follicle when compared with those of control samples. Our results suggest that the iodide transport system in the thyroid follicle is inhibited at 200 microM hydrogen peroxide or greater.
Fukayama
H
H
Division of Endocrinology and Metabolism, Wadsworth VA Hospital, Los Angeles, California.
Murakami
S
S
Nasu
M
M
Sugawara
M
M
D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D007455:Iodine / Q000493:pharmacokinetics*; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis; D013552:Swine; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism*
D007455:Iodine; D006861:Hydrogen Peroxide; D000242:Cyclic AMP; D000254:Sodium-Potassium-Exchanging ATPase