title: Characterization of testicular expression of P450 17α-hydroxylase, 17,20-lyase in zebrafish and its perturbation by the pharmaceutical fungicide clotrimazole.
abstract: The aim of the present study was to characterize P450 17α-hydroxylase/17,20-lyase (cyp17a1) expression in zebrafish and to assess the effect of the pharmaceutical clotrimazole, a known inhibitor of various cytochrome P450 enzyme activities, on testicular gene and protein expression of this enzyme as well as on the testicular release of 11-ketotestosterone (11-KT), a potent androgen in fish. We first showed that cyp17a1 is predominantly expressed in gonads of zebrafish, notably in male. In vivo, clotrimazole induced a concentration-dependent increase of cyp17a1 gene expression and Cyp17-I protein synthesis in zebrafish testis. Using zebrafish testicular explants, we further showed that clotrimazole did not directly affect cyp17a1 expression but that it did inhibit 11-KT release. These novel data deserve further studies on the effect of azole fungicides on gonadal steroidogenesis.
authors.affiliation: Institut National de l'environnement industriel et des risques (INERIS), Direction des Risques Chroniques, Unité d'écotoxicologie in vitro et in vivo, BP 2, 60550 Verneuil-en-Halatte, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Hinfray
authors.forename: Damien
authors.initials: D
authors.lastname: Baudiffier
authors.forename: Marcelo C
authors.initials: MC
authors.lastname: Leal
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Porcher
authors.forename: Sélim
authors.initials: S
authors.lastname: Aït-Aïssa
authors.forename: Florence
authors.initials: F
authors.lastname: Le Gac
authors.forename: Rüdiger W
authors.initials: RW
authors.lastname: Schulz
authors.forename: François
authors.initials: F
authors.lastname: Brion
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002478:Cells, Cultured; D003022:Clotrimazole / Q000494:pharmacology*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006066:Gonads / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D061251:Primary Cell Culture; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics* / Q000378:metabolism; D013737:Testis / Q000737:chemistry / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D013739:Testosterone / Q000031:analogs & derivatives / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D000935:Antifungal Agents; D029961:Zebrafish Proteins; D013739:Testosterone; D013254:Steroid 17-alpha-Hydroxylase; C000607915:cyp17a1 protein, zebrafish; D003022:Clotrimazole; C003600:11-ketotestosterone