Differential expression of sulfotransferase enzymes involved in thyroid hormone metabolism during human placental development

被引:62
作者
Stanley, EL
Hume, R
Visser, TJ
Coughtrie, MWH [1 ]
机构
[1] Univ Dundee, Ninewells Hosp & Med Sch, Dept Mol & Cellular Pathol, Dundee DD1 9SY, Scotland
[2] Univ Dundee, Ninewells Hosp & Med Sch, Dept Obstet & Gynaecol, Dundee DD1 9SY, Scotland
[3] Erasmus Univ, Sch Med, Dept Internal Med, NL-3015 GD Rotterdam, Netherlands
关键词
D O I
10.1210/jc.86.12.5944
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Thyroid hormone is essential for normal human development, and disruption of thyroid hormone homeostasis at critical developmental stages can result in severe and often long-term effects on crucial organs such as the brain and lungs. Numerous factors control the bioavailability of receptor active thyroid hormone T-3. Sulfation, catalyzed by sulfotransferase enzymes (SULTs), is an important pathway of thyroid hormone metabolism by which T-4 is irreversibly converted to inactive reverse T-3 rather than active T-3. The human fetus and neonate have high levels of circulating sulfated iodothyronines, although the source of these is not clear. The placenta forms the link between the fetus and its mother and is involved in transfer of thyroid hormone early in pregnancy, although its capacity for sulfation is unknown. We therefore examined expression of the SULTs involved in iodothyronine metabolism during human placental development. SULT activity was measured in human placental cotyledon and membranes (amnion, chorion, and decidua basalis) from 13-42 wk of gestation, and Western blot analysis was employed to verify enzyme activity data. Phenol and catecholamine sulfotransferases were expressed at the highest levels and were generally higher in the villous than membranous tissues. SULT1A1 activity showed significant correlation with sulfation of 3,3'-T-2, suggesting that this enzyme is primarily responsible for placental T-2 sulfation. Estrogen sulfotransferase was present at extremely low levels during early pregnancy, although in mid- and late gestation increased expression in the (predominantly maternal-derived) decidual component of the placenta was observed. Hydroxysteroid sulfotransferase, T-3, reverse T-3, and T-4 SULT activities were also low in all tissues examined and expression of SULTs 1B1 and 1C2 were essentially undetectable by Western blot analysis. The results highlight a tissue-specific regulation of SULT expression during placental development, demonstrate very low sulfation of iodothyronines suggesting that the placenta is not a major source of circulating sulfated iodothyronines in the fetus.
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页码:5944 / 5955
页数:12
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