Metabolism of 4-hydroxyandrost-4-ene-3,17-dione by rat hepatocytes

4-[14C]HAD was rapidly metabolized (99% after 5 min) by hepatocytes from phenobarbital-treated rats. An array of phase I metabolites was formed, variously involving one and two reductions, hydroxylation, hydration and hydroxylation plus one or two reductions. Some of the metabolites were identified by synthesis and others tentatively by mass spectrometry. After 10 min, approximately 30% of the original radioactivity was present in HAD glucuronide and, after 15 min, approximately 60% was present in the total glucuronide fraction which contained several components. Only one of the phase I metabolites (2-hydroxy-HAD) exhibited significant aromatase inhibitory activity (45% of that of HAD).