INDUCTION OF TYPE-III DEIODINASE ACTIVITY IN ASTROGLIAL CELLS BY THYROID-HORMONES

被引:44
作者
ESFANDIARI, A [1 ]
COURTIN, F [1 ]
LENNON, AM [1 ]
GAVARET, JM [1 ]
PIERRE, M [1 ]
机构
[1] INSERM, UNITE RECH GLANDE THYROIDE & REGULAT HORMONALE, U96, 80 RUE GEN LECLERC, F-94276 LE KREMLIN BICETRE, FRANCE
关键词
D O I
10.1210/en.131.4.1682
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The type III deiodinase (D-III) activity in astroglial cells is induced by multiple pathways activated by cAMP, 12-O-tetradecanoylphorbol-13-acetate (TPA), and fibroblast growth factors (FGFs). This study examines the effects of thyroid hormones on D-111 activity in astroglial cells with or without induction by these factors. Addition of 10 nm T3 to the culture medium caused a slow increase in D-III activity, which reached a plateau after 48 h. This increase was concentration dependent (maximal response at 10 nm). Doses as low as 0.3 nm caused significant increases in D-III activity. The effect of T3 was reversible. A dose of 10 nM L-T3 D-T3, T4, 3,5,3'-triiodothyroacetic, or 3'-isopropyl-3,5-diiodothyronine produced 5- to 15-fold increases in D-III activity after 48 h. In contrast, 10 nM L-thyronine, 3-monoiodothyronine, 3,3'-diiodothyronine, 3,5-diiodothyronine, and rT3 were without effect. A dose of 10 nm T3 or T4 amplified the D-III activity stimulated by 0.1 mum TPA, 20 ng/ml acidic FGF, or 1 mm 8-bromo-cAMP 3- to 8-fold. Otherwise, T3 rapidly inhibited D-11 activity. This inhibition was concentration dependent, with a half-maximal effect around 10 nm. In conclusion, thyroid hormones induce D-III activity and potentiate the D-III activity induced by cAMP, TPA, and FGFs in astroglial cells. These reversible effects together with inhibition of D-II activity may contribute to protect the brain against hyperthyroidism.
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页码:1682 / 1688
页数:7
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