抑制垂体甲状腺素向3,5,3'-三碘甲状腺原氨酸的转化可防止甲状腺功能减退大鼠中甲状腺素对促甲状腺激素释放的急性抑制作用。
Inhibition of intrapituitary thyroxine to 3.5.3'-triiodothyronine conversion prevents the acute suppression of thyrotropin release by thyroxine in hypothyroid rats.
作者信息
Larsen P R, Dick T E, Markovitz B P, Kaplan M M, Gard T G
出版信息
J Clin Invest. 1979 Jul;64(1):117-28. doi: 10.1172/JCI109430.
Iopanoic acid has been shown to block thyroxine (T4)-5'-monodeiodination in rat anterior pituitary in vitro. To test the hypothesis that the acute decrease in thyrotropin (TSH) after infusion of T4 into hypothyroid rats requires intrapituitary T4 to 3,5,3'-triiodothyroxine (T3) conversion, the effect of iopanoic acid treatment on the generation of nuclear T3 from intrapituitary conversion and the response to TSH were compared in control and iopanoic acid-treated animals. 5 mg/100 g body weight iopanoic acid given 24, 16, and 1.5 h before administration of 125I-T4 reduced the quantity of pituitary nuclear 125I-T3 from local (intrapituitary) T4 to T3 conversion by 60-100%. In association with inhibition of intrapituitary T4 to T3 conversion, there was an increase in the binding of 125I-T4 to the nuclear receptor of the pituitary but the total iodothyronine content of the nuclei was still less than half of the nuclear iodothyronine in control animals. Iopanoic acid did not affect the nuclear/plasma ratio of injected 131I-T3 in the same animals, but did appear to impair 131I-T3 clearance or reduce its distribution volume. Treatment with iopanoic acid did not reduce the quantity of nuclear 125I-T3 in the liver, kidney, or heart of the same animals more than expected from the changes in serum 125I-T3. In control hypo-thyroid animals pretreated with iopanoic acid, the mean TSH was not significantly decreased from the initial value by T4 injection. Iopanoic acid pretreatment did not interfere with the acute TSH response of chronically hypothyroid rats to 70 ng of T3/100 g body weight. These results establish that intrapituitary generations of T3 from T4 is required for the acute decrease in TSH which occurs after T4 infusion. The data also are consistent with the content that it is nuclear binding of the T3 generated from T4 which initiates the inhibition of TSH release.
已证明碘番酸在体外可阻断大鼠垂体前叶中甲状腺素（T4）的5'-单脱碘作用。为了验证甲状腺功能减退大鼠输注T4后促甲状腺激素（TSH）急性下降需要垂体内部将T4转化为3,5,3'-三碘甲状腺原氨酸（T3）这一假说，在对照动物和经碘番酸处理的动物中比较了碘番酸处理对垂体内部转化产生核T3的影响以及对TSH的反应。在给予125I-T4前24、16和1.5小时给予5mg/100g体重的碘番酸，可使垂体核内由局部（垂体内部）T4向T3转化产生的125I-T3量减少60%-100%。与垂体内部T4向T3转化的抑制相关，125I-T4与垂体核受体的结合增加，但核内总碘甲状腺原氨酸含量仍不到对照动物核内碘甲状腺原氨酸的一半。碘番酸对同一动物体内注射的131I-T3的核/血浆比值没有影响，但似乎确实损害了131I-T3的清除或降低了其分布容积。碘番酸处理并未使同一动物肝脏、肾脏或心脏中的核125I-T3量减少超过血清125I-T3变化所预期的程度。在用碘番酸预处理的对照甲状腺功能减退动物中，T4注射并未使平均TSH从初始值显著降低。碘番酸预处理并未干扰长期甲状腺功能减退大鼠对70ng T3/100g体重的急性TSH反应。这些结果表明，T4在垂体内部转化为T3是T4输注后TSH急性下降所必需的。数据还与以下观点一致，即T4产生的T3的核结合启动了TSH释放的抑制。
Zotero 插件