THYROID-HORMONES AND THE HEPATIC HANDLING OF BILIRUBIN .1. EFFECTS OF HYPOTHYROIDISM AND HYPERTHYROIDISM ON THE HEPATIC TRANSPORT OF BILIRUBIN MONO-CONJUGATE AND DICONJUGATE IN THE WISTAR RAT
THYROID-HORMONES AND THE HEPATIC HANDLING OF BILIRUBIN .1. EFFECTS OF HYPOTHYROIDISM AND HYPERTHYROIDISM ON THE HEPATIC TRANSPORT OF BILIRUBIN MONO-CONJUGATE AND DICONJUGATE IN THE WISTAR RAT
复制标题
DOI：
10.1002/hep.1840090225
复制
发表时间：
1989-02-01
期刊：
影响因子：
13.5
通讯作者：
DEGROOTE, J
中科院分区：
文献类型：
--
作者：
VANSTEENBERGEN, W;FEVERY, J;DEGROOTE, J
在 Wistar R/APfd 大鼠中研究了甲状腺切除术和甲状腺激素给药对内源性胆红素肝脏转运的影响。甲状腺功能减退症导致肝胆红素UDP-葡萄糖醛酸基转移酶活性增强，而对硝基苯酚转移酶活性降低。它会导致胆汁淤积，胆汁流量和胆汁盐排泄减少 50%，血清中结合胆红素的比例增加。非结合胆红素和单结合胆红素的胆汁输出量同时下降约 65%，而双结合胆红素的排泄率仅下降 47%，导致胆汁中双结合胆红素与单结合胆红素的比例增加。甲状腺功能亢进症的特征是胆红素减少和对硝基苯酚转移酶活性增加，以及胆汁中胆红素输出增加。非结合胆红素和单结合胆红素的输出量同时增加约 50% 或 100%，而双结合胆红素的排泄量仅增加 20% 至 50%，具体取决于甲状腺素的给药剂量；这导致胆汁中双结合物与单结合物的比率降低。胆红素UDP-葡萄糖醛酸基转移酶活性与胆汁中存在的或在低浓度胆红素（10至15μM）下体外培养肝匀浆形成的胆红素二结合物与单结合物的比率之间发现线性正相关关系，表明胆色素组成主要由肝脏中的结合活性决定。观察到的肝 β-葡萄糖醛酸酶活性与胆汁中双结合物与单结合物的比率之间的负相关关系值得进一步研究，以分析该酶活性是否也在甲状腺功能减退和甲状腺功能亢进大鼠的胆汁色素成分变化中发挥作用。
The effects of thyroidectomy and of thyroid hormone administration on the hepatic transport of endogenous bilirubin were investigated in the Wistar R/APfd rat. Hypothyroidism resulted in an enhanced hepatic bilirubin UDP-glucuronosyltransferase activity and in a decreased p-nitrophenol transferase activity. It caused a cholestatic condition with a 50% decrease in bile flow and bile salt excretion, and an increased proportion of conjugated bilirubin in serum. The biliary output of unconjugated and monoconjugated bilirubins decreased in parallel by about 65%, whereas the excretion rate of the diconjugate dropped by only 47%, resulting in an increased di-to monoconjugate ratio in bile. Hyperthyroidism was characterized by a decreased bilirubin and an increased p-nitrophenol transferase activity, and by an augmented bilirubin output in bile. The output of unconjugated and monoconjugated bilirubins increased in parallel by about 50 or 100%, whereas the excretion of the diconjugate increased by only 20 to 50%, depending on the dose of thyroxine administered; this resulted in a decreased di-to monoconjugate ratio in bile. A linear positive relationship was found between bilirubin UDP-glucuronosyltransferase activity and the ratio of bilirubin di-to monoconjugates present in bile or formed by in vitro incubation of liver homogenates at low concentration of bilirubin (10 to 15 μM), indicating that bile pigment composition is mainly determined by the conjugation activity in the liver. The inverse relationship observed between hepatic β-glucuronidase activity and the ratio of di-to monoconjugates in bile warrants further investigation to analyze whether this enzyme activity also plays a possible role in the changes in bile pigment composition in hypo-and hyperthyroid rats.