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

Fernandes, Denise; Bebianno, Maria João; Porte, Cinta

http://hdl.handle.net/10400.1/13853

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Authors

Fernandes, Denise

Bebianno, Maria João

Porte, Cinta

Abstract(s)

The metabolism of 17alpha-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 (11beta-hydroxylase) catalyzed reactions was demonstrated in the mitochondrial fraction, where 17P(4) was converted to androstenedione (AD) and further metabolized to 11beta-hydroxyandrostenedione (betaAD). The synthesis of betaAD predominated in early spermatogenic testis, indicating a role of betaAD 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 microM NP inhibited the activity of CYP17 (C17,20-lyase) whereas 100 microM 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.

Keywords

17-alpha-hydroxyprogesterone Animals Bass Benz(a) anthracenes Dichlorodiphenyl dichloroethylene Endocrine disruptors Gas chromatography-mass spectrometry Histocytochemistry Male Mitochondria Phenols Steroid 11-beta-hydroxylase Steroid 17-alpha-hydroxylase Testis Trialkyltin compounds Water pollutants Chemical