SULFATION AFTER DEIODINATION OF 3,5,3'-TRIIODOTHYRONINE IN RAT CULTURED ASTROCYTES

被引:13
作者
ESFANDIARI, A [1 ]
GAVARET, JM [1 ]
LENNON, AM [1 ]
PIERRE, M [1 ]
COURTIN, F [1 ]
机构
[1] INSERM, U-96, F-94276 LE KREMLIN BICETRE, FRANCE
关键词
D O I
10.1210/en.135.5.2086
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The metabolism of [I-125]T-3 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'T-2) sulfate (3,3'T-2-S) was the main product that accumulated in the medium over the T-3 concentration explored (10 pM to 10 nM). The identity of the peak eluted as 3,3'T-2-S was ascertained by its hydrolysis with sulfatase and the generation of 3,3'T-2 identified by HPLC. 3'-Monoiodothyronine sulfate was also found in cells treated with 1 mu M retinoic acid, i.e. with high type III deiodinase activity. No T-3 sulfate (T-3-S) was found as a metabolite of T-3. Astrocytes did not break down 1 nM [I-125]T-3-S added to the medium. Astrocytes pretreated for 3 days with 10 nM T-3 showed increased production of 3,3'T-2-S from 10 nM [I-125]T-3. Exogenous [I-125]3,3'T-2 (20 nM) was conjugated to 3,3'T-2-S released into the medium, Pretreatment of astrocytes with 10 nM T-3 did not alter the production of 3,3'T-2-S from 3,3'T-2. Thus, T-3 is metabolized in astrocytes by direct 5-deiodination, followed by sulfation. Whereas T-3 induces its own deiodination and type III deiodinase activity, T-3 does not regulate the sulfation of its main metabolite, 3,3'T-2. 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.
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页码:2086 / 2092
页数:7
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