Suppression of bile acid synthesis by thyroid hormone in primary human hepatocytes  

作　　者：Ewa Cristine Siljevik Ellis 

机构地区：[1]Department of Medicine Division of Gastroenterology and Hepatology,and the Department of Laboratory Medicine,Division of Clinical Chemistry,Karolinska University Hospital at Huddinge,Karolinska Institute,Stockholm,Sweden

出　　处：《World Journal of Gastroenterology》2006年第29期4640-4645,共6页世界胃肠病学杂志（英文版）

基　　金：the Swedish Research Council, the Karolinska Institute and the Swedish Society for Medical Research

摘　　要：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 （T3） 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 T3. Bile acid formation and mRNA levels of key enzymes were analysed. RESULTS： The lowest concentration of T3 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 of mRNA levels of cholesterol 7α-hydroxylase （CYP7A1） and sterol 12α-hydroxylase （CYPSB1） dose-dependently decreased. Sterol 27-hydroxylase （CYP27A1） levels also decreased, but not to the same extent. CONCLUSION： T3 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.瞄准：甲状腺激素在人改变胆汁酸新陈代谢，这被知道，然而，单个酶上的效果是困难的阐明。这主要由于生产胆汁酸的人的肝房间线的缺乏。我们使用了主要人的 hepatocytes 的文化在胆汁酸合成上学习三碘甲状腺氨酸(T (3 )) 的效果。方法：主要 hepatocytes 从从由于内在的恶意经历肝切除术的三个不同病人获得的肝织物被孤立。hepatocytes 在没有浆液的条件下面是有教养的并且从 d 对待 1 到 d 5 与包含 0.1 的文化 - T (3 ) 的 1000 nmol/L。关键酶的胆汁酸形成和 mRNA 层次被分析。结果：T (3 ) 的最低集中减少了胆酸(CA ) 形成到到 d 上的控制的 52%-75% 的控制和 chenodeoxycholic 酸(CDCA ) 的 43%-53% 5。最高的剂量当 CDCA 形成在控制的 50%-117% 留下了时，推进减少的 CA 形成到控制的 16%-48% 。胆固醇 7alpha-hydroxylase (CYP7A1 ) 和甾醇 12alpha-hydroxylase (CYP8B1 ) 的 mRNA 层次的表示 dose-dependently 减少了。甾醇 27-hydroxylase (CYP27A1 ) 层次也减少了，然而并非到一样的程度。结论：T (3 ) dose-dependently 减少了与 CYP7A1 和 CYP8B1 的减少的表示同时的全部的胆汁酸形成。CA 形成比 CDCA 被禁止到更高的度，导致在 CA /CDCA 比率的显著减少。

关 键 词：HEPATOCYTES HUMAN Bile acids CYP7A1 CYPSB1 CYP27A1 

分 类 号：R575[医药卫生—消化系统]