Little J M, St Pyrek J, Lester R
J Clin Invest. 1983 Jan;71(1):73-80. doi: 10.1172/jci110753.
Normal human meconium has been shown to contain short-chain (C20-C22) bile acids and, recently, these compounds have been identified in sera of patients with cholestasis. This suggests that shortchain bile acids may be secreted in bile. We have examined this point by studying the hepatic metabolism and biliary secretion of one naturally occurring C20 bile acid, 3 alpha-hydroxy-5 beta-etianic acid (3 alpha-hydroxy-5 beta-androstan-17 beta-carboxylic acid). [3-3H]-3 alpha-hydroxy-5 beta-etianic acid was prepared and administered intravenously to rats prepared with an external biliary fistula. 85.5 +/- 1.2% of the administered dose was recovered in bile over 20 h with 71.5 +/- 1.3% appearing in the first hour. 11.9 +/- 1.6% of the dose was estimated to be distributed in body water and 0.6 +/- 0.2% was recovered as organic matter in urine. Total recovery of label was 98.0 +/- 2.6%. Administration of milligram quantities of 3 alpha-hydroxy-5 beta-etianic acid produced an increase in bile flow (58.9 +/- 7.1% over basal levels) within 20 min after injection of the steroid. The radiolabeled material in bile was shown by thin-layer chromatography (TLC) to be a polar conjugate which, after beta-glucuronidase hydrolysis, cochromatographed with authentic free 3 alpha-hydroxy-5 beta-etianic acid. After purification, and derivatization, the steroid moiety was proven by gas chromatography-mass spectrometry to be identical to 3 alpha-hydroxy-5 beta-etianic acid. Characterization of the conjugate by TLC and by 3 alpha-hydroxysteroid dehydrogenase assay, before and after beta-glucuronidase hydrolysis, indicated that the steroid was secreted in bile as the 3-O-beta-glucuronide. It is concluded that 3 alpha-hydroxy-5 beta-etianic acid is cleared from the plasma, conjugated with glucuronic acid, and secreted into bile rapidly and in high concentration. The choleretic properties of this shortchain bile acid contrast with the cholestatic effects of lithocholic acid, its C24 analog. Both the form of conjugation of etianic acid and its effect on bile flow suggest that the shortened side chain of this steroid markedly alters its hepatic metabolism and physiology.
已证实正常人类胎粪中含有短链（C20 - C22）胆汁酸，最近在胆汁淤积患者的血清中也发现了这些化合物。这表明短链胆汁酸可能会分泌到胆汁中。我们通过研究一种天然存在的C20胆汁酸——3α - 羟基 - 5β - 孕甾烷酸（3α - 羟基 - 5β - 雄甾烷 - 17β - 羧酸）的肝脏代谢和胆汁分泌来探讨这一问题。制备了[3 - 3H] - 3α - 羟基 - 5β - 孕甾烷酸，并将其静脉注射给制备了外引流胆汁瘘的大鼠。给药剂量的85.5±1.2%在20小时内从胆汁中回收，其中71.5±1.3%在第一小时出现。估计给药剂量的11.9±1.6%分布在体液中，0.6±0.2%以有机物质形式从尿液中回收。标记物的总回收率为98.0±2.6%。注射毫克量的3α - 羟基 - 5β - 孕甾烷酸后20分钟内胆汁流量增加（比基础水平增加58.9±7.1%）。胆汁中的放射性标记物质经薄层色谱法（TLC）显示为一种极性共轭物，经β - 葡萄糖醛酸酶水解后，与 authentic free 3α - 羟基 - 5β - 孕甾烷酸共色谱。纯化和衍生化后，通过气相色谱 - 质谱法证明甾体部分与3α - 羟基 - 5β - 孕甾烷酸相同。在β - 葡萄糖醛酸酶水解前后，通过TLC和3α - 羟基甾体脱氢酶测定对共轭物进行表征，表明该甾体以3 - O - β - 葡萄糖醛酸苷形式分泌到胆汁中。结论是3α - 羟基 - 5β - 孕甾烷酸从血浆中清除，与葡萄糖醛酸结合，并迅速且高浓度地分泌到胆汁中。这种短链胆汁酸的利胆特性与其C24类似物石胆酸的胆汁淤积作用形成对比。孕甾烷酸的共轭形式及其对胆汁流量的影响均表明，这种甾体缩短的侧链显著改变了其肝脏代谢和生理学特性。
