Nasu M, Sugawara M
Medical Service, Wadsworth Veterans Administration Medical Center, Los Angeles, California 90073.
Endocrinology. 1993 Jan;132(1):155-60. doi: 10.1210/endo.132.1.8380371.
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.
我们描述了在生理培养系统中乙醇对甲状腺激素形成的促甲状腺激素（TSH）样活性。将猪甲状腺滤泡在0 - 1280微单位/毫升牛TSH存在的情况下，用0 - 100毫摩尔/升（0 - 0.58%）乙醇预孵育24小时；然后将这些滤泡与碘化钠（Na125I）和碘化钠（NaI）的混合物一起孵育，以测量碘摄取、碘有机化和甲状腺激素的从头合成。在无TSH的培养基中，乙醇以剂量反应方式刺激碘摄取。在20 - 80微单位/毫升TSH存在的情况下，乙醇增强了TSH对碘摄取、碘有机化和甲状腺激素形成的作用。当TSH浓度为320微单位/毫升或更高时，乙醇不再刺激碘摄取和甲状腺激素形成。乙醇介导的碘摄取和碘有机化分别被高氯酸钾和丙硫氧嘧啶抑制。从培养基中去除乙醇24小时后，乙醇对甲状腺滤泡的作用是可逆的。通过在0 - 1280微单位/毫升TSH存在的情况下测量环磷酸腺苷（cAMP）生成和钠钾ATP酶活性（碘转运所需的钠泵），研究了乙醇的TSH样活性机制。乙醇在无TSH的培养基中增加了cAMP的产生；当存在20 - 80微单位/毫升TSH时，乙醇引起的cAMP增加更为显著。乙醇还增强了双丁酰环磷腺苷（Bu）2cAMP介导的碘摄取和TSH介导的甲状腺钠钾ATP酶活性。因此，乙醇对甲状腺激素形成的TSH样活性可以通过cAMP系统和钠钾ATP酶活性的激活来解释。我们的结果表明，与中度至重度饮酒者血液水平相当的乙醇浓度在甲状腺滤泡中发挥TSH样活性。
