Metabolism of the 16-androstene steroids in primary cultured porcine hepatocytes.
The hepatic metabolism of the 16-androstene steroids was investigated using isolated porcine hepatocytes. This study demonstrated that the liver is capable of producing both phase I and phase II steroid metabolites from 16-androstene steroid precursors. 16-Androstene metabolites were recovered by solid-phase extraction and identified by gas chromatography-mass spectrometry (GC-MS). When 5alpha-androstenone was provided as a substrate, both 3beta- and 3alpha-androstenol were produced as well as a metabolite that showed evidence of hydroxylation. Incubations with the various 16-androstene steroids produced metabolic profiles which suggested that the major role of the liver is phase II conjugation. Sulfoconjugated 16-androstene steroids included androstadienol, 5alpha-androstenone, 3beta-, 3alpha-androstenol, and possibly the hydroxylated metabolite of 5alpha-androstenone. It was determined that hydroxysteroid sulfotransferase (HST) is the likely candidate for the sulfoconjugation of the 16-androstene steroids within the liver. Despite the capacity of the hepatocytes to sulfoconjugate the 16-androstene steroids, the principle metabolites produced from incubations with 5alpha-androstenone, 3beta-, and 3alpha-androstenol were glucuronide conjugates, accounting for approximately 68% of all phase II metabolism. These findings underline the importance of steroid conjugation and suggest that hepatic metabolism of the 16-androstene steroids may influence the levels of 5alpha-androstenone present in the circulation, and thus, capable of accumulating in fat.
Sinclair
P A
PA
Department of Animal and Poultry Science, University of Guelph, Guelph, Ontario, Canada N1G 2W1.
Hancock
S
S
Gilmore
W J
WJ
Squires
E J
EJ
D000736:Androstenes / Q000378:metabolism*; D000818:Animals; D002478:Cells, Cultured; D008401:Gas Chromatography-Mass Spectrometry; D022781:Hepatocytes / Q000378:metabolism*; D007700:Kinetics; D013552:Swine
D000736:Androstenes; C042468:16-androstene