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

• Published in: Steroids Vol. 57; no. 7; p. 328
• Main Authors: Radominska, A, Little, J M, Lester, R, St Pyrek, J
• Format: Journal Article
• Language: English
• Published: United States 01-07-1992
• Subjects: 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
• ISSN: 0039-128X
• DOI: 10.1016/0039-128X(92)90052-B

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.