Hepatic metabolism of 3 alpha-hydroxy-5 beta-etianic acid (3 alpha-hydroxy-5 beta-androstan-17 beta-carboxylic acid) in the adult rat.

Abstract

A B S T R A C T 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, 3a-hydroxy-5,3-etianic acid (3a-hydroxy-5fB-androstan-17f3-carboxylic acid).[3-3H]-3a-hydroxy-5,3-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 3a-hydroxy-5#3-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 thinlayer chromatography (TLC) to be a polar conjugate which, after 13-glucuronidase hydrolysis, cochromatographed with authentic free 3a-hydroxy-5f3-etianic acid. After purification, and derivatization, the steroid moiety was proven by gas chromatography-mass spectrometry to be identical to 3a-hydroxy-513-etianic acid.Characterization of the conjugate by TLC and by 3a-hydroxysteroid dehydrogenase assay, before and after 3-glucuronidase hydrolysis, indicated that the steroid was secreted in bile as the 3-O-f3-glucuronide.These results were presented in part at the Annual Meeting of the American Society for Clinical Investigation, Washington, DC, 8 May 1982, and were published in abstract form (Clin. Res. 30: 497a).Received for publication 7 June 1982 and in revised form 28 September 1982. It is concluded that 3a-hydroxy-5f-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. INTRODUCTION The bile acids are bioactive compounds that serve essential normal digestive functions and have disruptive effects when they accumulate in tissues in excess. Although bile acids frequently are considered a homogeneous group, each has peculiar physical characteristics and each is capable of exerting distinctive biological effects.The application of sophisticated computerized gas chromatography-mass spectrometry (GC-MS)' technology to the analysis of bile acids has increased the number and variety identified in biological materials. It is now recognized that the spectrum of naturally occurring compounds that have a hydroxylated steroid nucleus and an acidic side-chain is more co...

Human liver steroid sulphotransferase sulphates bile acids

“…A number of monohydroxylated short-chain bile acids has been identified in the developing organism and also, but to a lesser extent, in the adult [38][39][40]. They are known to be secreted as glucuronides [41,42]. Since some short-chain bile acids are metabolically derived from steroid hormones, their analysis may be important to the understanding of hormone turnover and balance.…”

Metabolism of 24-norlithocholic acid in the rat: Formation of hydroxyl- and carboxyl-linked glucuronides and effect on bile flow

“…Similar results were observed in uiuo with C20 BA. This indicates that, for 3a-hydroxylated 5P-H BA, reversible oxidation of the hydroxyl group is not significant in the liver of the rat (20). It has been shown in anaerobically grown Clostridium that a small but significant fraction of 'H is retained in the 3 position of BA after an oxidation-reduction cycle, probably because the same molecule of NAD' accepts and later donates the hydrogen atom in a situation where the pool of coenzyme is limited (21).…”

Nature of Bile Acids in the Fetus and Newborn Infant

“…However, several bits of information are available and can be described briefly. Certain 20 carbon bile acids found in human meconium have been radiochemically labeled and administered intravenously to rats prepared with a bil iary fistula (47,48). These shortchain bile acids, 1 ike typical bile acids, are cleared from plasma and secreted in bile with a high degree of efficiency.…”