Mitochondrial metabolism of 17α-hydroxyprogesterone in male sea bass ( Dicentrarchus labrax): A potential target for endocrine disruptors

Abstract

The metabolism of 17α-hydroxyprogesterone (17P 4) was investigated in different subcellular fractions isolated from male gonads of sea bass ( Dicentrarchus labrax L). The existence of CYP17 (C17,20-lyase activity) and CYP11B (11β-hydroxylase) catalyzed reactions was demonstrated in the mitochondrial fraction, where 17P 4 was converted to androstenedione (AD) and further metabolized to 11β-hydroxyandrostenedione (βAD). The synthesis of βAD predominated in early spermatogenic testis, indicating a role of βAD in testicular recrudescence. Additionally, the in vitro effect of model endocrine disrupting chemicals (i.e. nonylphenol (NP), p, p′-DDE, benzo[a]anthracene (BaA), tributyltin (TBT) and ketoconazole (KCZ)) on the mitochondrial metabolism of 17P 4 was investigated. Among the tested compounds, 100 μM NP inhibited the activity of CYP17 (C17,20-lyase) whereas 100 μM KCZ inhibited both CYP17 and CYP11B. Both chemicals showed the potential to disrupt the reproductive cycle of fish living in polluted environments due to impairment of testicular steroid biosynthesis. These results suggest that mitochondrial metabolism of 17P 4 may constitute a new sensitive probe for the assessment of endocrine disruption in fish.