Hepatic metabolism of 3-oxoandrost-4-ene-17 beta-carboxylic acid in the adult rat: formation of carboxyl-linked glucuronides both in vivo and in vitro

Steroids. 1992 Jul;57(7):328-34. doi: 10.1016/0039-128x(92)90052-b.

Abstract

The hepatic metabolism of 3-oxoandrost-4-ene-17 beta-carboxylic acid (etienic acid), a probable acidic catabolite of deoxycorticosterone, was investigated using rats prepared with an external biliary fistula. Metabolic products were identified by GC-MS after hydrolysis with beta-glucuronidase and by proton nuclear magnetic resonance after chromatographic purification of protected glucuronides. About 80% of the injected dose was secreted into bile in 20 hours. Three fully reduced etianic acids (3 alpha-hydroxy-5 alpha-, 3 beta-hydroxy-5 alpha-, 3 alpha-hydroxy-5 beta-androstan-17 beta-carboxylic acids) were identified as were several of their di- and trihydroxylated congeners. Glucuronides of these reduced and/or hydroxylated metabolites constituted over half of the recovered dose, with carboxyl-linked glucuronides predominating over 3-hydroxyl-linked glucuronides. The mode of glucuronidation correlated well with the ability of liver microsomes to form the corresponding compounds in vitro from the set of four 3,5-diastereomeric etianic acids.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Androstenes / chemistry
  • Androstenes / metabolism*
  • Animals
  • Bile / metabolism
  • Gas Chromatography-Mass Spectrometry
  • Glucuronates / metabolism*
  • Glucuronidase / metabolism
  • Hydrolysis
  • Liver / metabolism*
  • Magnetic Resonance Spectroscopy
  • Male
  • Molecular Structure
  • Rats
  • Rats, Inbred Strains

Substances

  • Androstenes
  • Glucuronates
  • etienic acid
  • Glucuronidase