Mitochondrial metabolism of 17alpha-hydroxyprogesterone in male sea bass (Dicentrarchus labrax): a potential target for endocrine disruptors.
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.
Fernandes
Denise
D
C.I.M.A., University of Algarve, F.C.M.A., Campus de Gambelas, 8005-139 Faro, Portugal.
Bebianno
Maria João
MJ
Porte
Cinta
C
D019326:17-alpha-Hydroxyprogesterone / Q000378:metabolism*; D000818:Animals; D001492:Bass / Q000378:metabolism*; D001551:Benz(a)Anthracenes / Q000494:pharmacology; D003633:Dichlorodiphenyl Dichloroethylene / Q000494:pharmacology; D052244:Endocrine Disruptors / Q000494:pharmacology*; D008401:Gas Chromatography-Mass Spectrometry; D006651:Histocytochemistry; D008297:Male; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology; D013252:Steroid 11-beta-Hydroxylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013254:Steroid 17-alpha-Hydroxylase / Q000037:antagonists & inhibitors / Q000378:metabolism; D013737:Testis / Q000201:enzymology / Q000378:metabolism*; D014220:Trialkyltin Compounds / Q000494:pharmacology; D014874:Water Pollutants, Chemical / Q000494:pharmacology*
D001551:Benz(a)Anthracenes; D052244:Endocrine Disruptors; D010636:Phenols; D014220:Trialkyltin Compounds; D014874:Water Pollutants, Chemical; D003633:Dichlorodiphenyl Dichloroethylene; C011559:tributyltin; D019326:17-alpha-Hydroxyprogesterone; C025256:nonylphenol; C030935:benz(a)anthracene; D013254:Steroid 17-alpha-Hydroxylase; D013252:Steroid 11-beta-Hydroxylase