Ethanol has thyrotropin-like activity in cultured porcine thyroid follicles

We describe TSH-like activity of ethanol for thyroid hormone formation in the physiological culture system. Porcine thyroid follicles were preincubated with 0-100 mM (0-0.58%) ethanol in the presence of 0-1280 microU/ml bovine TSH for 24 h; these follicles were then incubated with the mixture of Na125I and NaI to measure iodide uptake, iodine organification, and de novo thyroid hormone formation. Ethanol stimulated iodide uptake in a dose-response manner in TSH-free medium. Ethanol augmented the effect of TSH on iodide uptake, iodide organification, and thyroid hormone formation in the presence of 20-80 microU/ml TSH. When TSH concentration was 320 microU/ml or greater, ethanol no longer stimulated iodide uptake and thyroid hormone formation. Ethanol mediated iodide uptake and iodine organification were inhibited by potassium perchlorate and propylthiouracil respectively. The effect of ethanol on the thyroid follicle was reversible 24 h after removal of ethanol from the medium. The mechanism of TSH-like activity of ethanol was studied by measuring cAMP generation and Na+K+ATPase activity, a sodium pump necessary for iodide transport, in the presence of 0-1280 microU/ml TSH. Ethanol increased cAMP production in TSH-free medium; the increment of cAMP by ethanol was more prominent when 20-80 microU/ml TSH were present. Ethanol also augmented (Bu)2cAMP-mediated iodide uptake and TSH-mediated thyroid Na+K+ATPase activity. Thus, TSH-like activity of ethanol for thyroid hormone formation can be explained by activation of the cAMP system and Na+K+ATPase activity. Our results indicate that ethanol concentrations equivalent to the blood level of moderate to heavy alcohol drinkers exert TSH-like activity in the thyroid follicle.