Esfandiari A, Gavaret J M, Lennon A M, Pierre M, Courtin F
Institut National de la Santé et de la Recherche Médicale, Kremlin-Bicêtre, France.
Endocrinology. 1994 Nov;135(5):2086-92. doi: 10.1210/endo.135.5.7956931.
The metabolism of [125I]T3 by rat astrocytes in culture was analyzed by Sephadex LH-20 chromatography and HPLC. The conjugates isolated on LH-20 were not hydrolyzed by glucuronidase, indicating the absence of glucuroconjugates. 3,3'-Diiodothyronine (3,3'T2) sulfate (3,3'T2-S) was the main product that accumulated in the medium over the T3 concentration explored (10 pM to 10 nM). The identity of the peak eluted as 3,3'T2-S was ascertained by its hydrolysis with sulfatase and the generation of 3,3'T2 identified by HPLC. 3'-Monoiodothyronine sulfate was also found in cells treated with 1 microM retinoic acid, i.e. with high type III deiodinase activity. No T3 sulfate (T3-S) was found as a metabolite of T3. Astrocytes did not break down 1 nM [125I]T3-S added to the medium. Astrocytes pretreated for 3 days with 10 nM T3 showed increased production of 3,3'T2-S from 10 nM [125I]T3. Exogenous [125I]3,3'T2 (20 nM) was conjugated to 3,3'T2-S released into the medium. Pretreatment of astrocytes with 10 nM T3 did not alter the production of 3,3'T2-S from 3,3'T2. Thus, T3 is metabolized in astrocytes by direct 5-deiodination, followed by sulfation. Whereas T3 induces its own deiodination and type III deiodinase activity, T3 does not regulate the sulfation of its main metabolite, 3,3'T2. This demonstration of sulfation of iodothyronines in cells originating from the brain raises the question of the role of this TH metabolic pathway in the brain.
通过葡聚糖凝胶LH - 20色谱法和高效液相色谱法分析了培养的大鼠星形胶质细胞对[125I]T3的代谢情况。在LH - 20上分离得到的结合物不能被葡萄糖醛酸酶水解，表明不存在葡萄糖醛酸结合物。3,3'-二碘甲状腺原氨酸（3,3'T2）硫酸盐（3,3'T2 - S）是在所研究的T3浓度范围（10 pM至10 nM）内培养基中积累的主要产物。通过用硫酸酯酶水解并经高效液相色谱法鉴定生成的3,3'T2，确定了洗脱峰为3,3'T2 - S。在用1 microM视黄酸处理的细胞中，即具有高III型脱碘酶活性的细胞中，也发现了3'-单碘甲状腺原氨酸硫酸盐。未发现T3硫酸盐（T3 - S）作为T3的代谢产物。星形胶质细胞不会分解添加到培养基中的1 nM [125I]T3 - S。用10 nM T3预处理3天的星形胶质细胞显示，从10 nM [125I]T3产生的3,3'T2 - S增加。外源性[125I]3,3'T2（20 nM）与释放到培养基中的3,3'T2 - S结合。用10 nM T3预处理星形胶质细胞不会改变3,3'T2产生3,3'T2 - S的情况。因此，T3在星形胶质细胞中通过直接5 - 脱碘，随后硫酸化进行代谢。虽然T3诱导其自身的脱碘和III型脱碘酶活性，但T3并不调节其主要代谢产物3,3'T2的硫酸化。在源自脑的细胞中碘甲状腺原氨酸硫酸化的这一证明提出了该甲状腺激素代谢途径在脑中作用的问题。
