Involvement of multiple biotransformation processes in the metabolic elimination of testosterone by juvenile and adult fathead minnows (Pimephales promelas).

Steroid hormone metabolic clearance pathways are susceptible to induction and suppression resulting from exposure to many xenobiotics. These biochemical effects have the potential to alter steroid hormone homeostasis and, ultimately, steroid hormone-dependent processes such as growth, development, and reproduction. In this study, the metabolic clearance of 17beta-hydroxy-4-androsten-3-one (testosterone) by adult male, adult female, and juvenile fathead minnows (Pimephales promelas) was evaluated. Individual elimination metabolites were identified and rates of metabolite elimination were quantified. Fathead minnows produced a variety of testosterone metabolites including oxido-reduced, hydroxylated, and conjugated derivatives. Metabolites identified by TLC/GC/MS included 4-androstene-3,17-dione (androstenedione), 17beta-hydroxy-5alpha-androstan-3-one (5alpha-dihydrotestosterone), 5alpha-androstane-3alpha,17beta-diol (3alpha-androstanediol), 5alpha-androstane-3beta,17beta-diol (3beta-androstanediol), 17beta-hydroxy-4-androstene-3,11-dione (11-ketotestosterone), 16beta-hydroxy-4-androsten-3-one (16beta-hydroxytestosterone), and 6beta-hydroxy-4-androsten-3-one (6beta-hydroxytestosterone). Testosterone and its metabolites were eliminated in both free and conjugated form. Adult male, adult female, and juvenile fathead minnows eliminated the same profile of testosterone metabolites. However, adult females eliminated androstanediols at a significantly greater rate than did males, and juvenile fish eliminated nearly all testosterone metabolites at greater weight-normalized rates than did adults. These results demonstrate that fathead minnows extensively metabolize testosterone leading to its elimination and provide the foundation upon which the effects of xenobiotics on testosterone metabolism can be assessed.