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.
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.
Radominska
A
A
Department of Internal Medicine, University of Arkansas for Medical Sciences, Little Rock 72205.
Little
J M
JM
Lester
R
R
St Pyrek
J
J
D000736:Androstenes / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D001646:Bile / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D005965:Glucuronates / Q000378:metabolism*; D005966:Glucuronidase / Q000378:metabolism; D006868:Hydrolysis; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D015394:Molecular Structure; D051381:Rats; D011919:Rats, Inbred Strains
D000736:Androstenes; D005965:Glucuronates; C004251:etienic acid; D005966:Glucuronidase