Biotransformation and branchial excretion of 17 alpha-methyltestosterone in trout

This study was designed to characterize the branchial excretion of 17 alpha-methyltestosterone (17MT) metabolites in rainbow trout (Oncorhynchus mykiss). Spinally transected trout were force-fed 0.4 mg/kg [1,2-3H]17MT and the branchial, fecal, and urinary excreta were collected during 24 hr. Branchial elimination was the primary route of excretion, because it contributed to 68% of the excreted radioactivity within 24 hr after ingestion. The radio-HPLC metabolic profile obtained from branchial excreta showed that 17MT was partly eliminated across the gills as parent compound. In addition to unchanged 17MT, several unconjugated metabolites have been isolated and identified by GC/MS. Two major pathways were involved in the biotransformation of 17MT: hydroxylation and/or reduction of the androstene structure. Reduction of the 4-ene functionality leading to the formation of methyldihydrotestosterone and its further reduction leading to the formation of methylandrostane-diol metabolites was observed. Other metabolites resulted from hydroxylation of 17MT at C-6 and C-7 positions and eventual further reduction of the 3-oxo-delta 4 group. They were tentatively assigned the structures of 17 alpha-methyl-4-androsten-6 beta,17 beta-ol-3-one, 17 alpha-methyl-4-androsten-7 xi,17 beta-ol-3-one, and 17 alpha-methyl-5-xi-androstan-3 xi,7 xi-triol. In addition, 17 alpha-methyl-4-androsten-17 beta-ol-3,11-dione and 17 alpha-methyl-17 beta-hydroxy-4,6-androstadiene-3-one were also identified and resulted probably from the oxidation of 11-hydroxy-17MT and dehydration of 6-hydroxy-17MT, respectively.