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首页> 外文期刊>World Journal of Gastroenterology >Suppression of bile acid synthesis by thyroid hormone in primary human hepatocytes.
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Suppression of bile acid synthesis by thyroid hormone in primary human hepatocytes.

机译：在原代人肝细胞中通过甲状腺激素抑制胆汁酸合成。

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AIM: It is known that thyroid hormones alter the bile acid metabolism in humans, however the effect on individual enzymes has been difficult to elucidate. This is mainly due to the lack of human liver cell lines producing bile acids. We used cultures of primary human hepatocytes to study the effects of triiodothyronine (T(3)) on bile acid synthesis. METHODS: Primary hepatocytes were isolated from liver tissue obtained from three different patients undergoing liver resection due to underlying malignancy. The hepatocytes were cultured under serum-free conditions and treated from d 1 to d 5 with culture containing 0.1 - 1000 nmol/L of T(3). Bile acid formation and mRNA levels of key enzymes were analysed. RESULTS: The lowest concentration of T(3) decreased cholic acid (CA) formation to 43%-53% of controls and chenodeoxycholic acid (CDCA) to 52%-75% of controls on d 5. The highest dose further decreased CA formation to 16%-48% of controls while CDCA formation remained at 50%-117% of controls. Expression ofmRNA levels of cholesterol 7alpha-hydroxylase (CYP7A1) and sterol 12alpha-hydroxylase (CYP8B1) dose-dependently decreased. Sterol 27-hydroxylase (CYP27A1) levels also decreased, but not to the same extent. CONCLUSION: T(3) dose-dependently decreased total bile acid formation in parallel with decreased expression of CYP7A1 and CYP8B1. CA formation is inhibited to a higher degree than CDCA, resulting in a marked decrease in the CA /CDCA ratio.
机译：目的：已知甲状腺激素会改变人类的胆汁酸代谢，但是很难阐明其对单个酶的作用。这主要是由于缺乏产生胆汁酸的人肝细胞系。我们使用原代人肝细胞的文化来研究三碘甲状腺素（T（3））对胆汁酸合成的影响。方法：从三名因潜在恶性肿瘤接受肝切除的患者的肝组织中分离出原代肝细胞。在无血清条件下培养肝细胞，并在d 1至d 5内用含0.1-1000 nmol / L的T（3）培养物处理。分析了胆汁酸的形成和关键酶的mRNA水平。结果：在第5天，最低浓度的T（3）可使胆酸（CA）形成减少至对照组​​的43％-53％，而鹅去氧胆酸（CDCA）则使对照组减少52％-75％。达到对照组的16％-48％，而CDCA的形成仍保持在对照组的50％-117％。胆固醇7α-羟化酶（CYP7A1）和固醇12α-羟化酶（CYP8B1）的mRNA表达呈剂量依赖性降低。甾醇27-羟化酶（CYP27A1）的水平也有所降低，但幅度不大。结论：T（3）剂量依赖性地降低总胆汁酸的形成，同时降低CYP7A1和CYP8B1的表达。与CDCA相比，CA的形成受到的抑制程度更高，从而导致CA / CDCA比值显着下降。

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