title: Can pharmaceuticals interfere with the synthesis of active androgens in male fish? An in vitro study.
abstract: The in vitro interference of fibrate (gemfibrozil, clofibrate, clofibric acid), anti-inflammatory (ibuprofen, diclofenac), and anti-depressive (fluoxetine, fluvoxamine) drugs with key enzymatic activities-C17,20-lyase and CYP11β-involved in the synthesis of active androgens in gonads of male carp have been investigated. Among the tested compounds, fluvoxamine and fluoxetine were the strongest inhibitors of C17,20-lyase and CYP11β enzymes, with IC50s in the range of 321-335 μM and 244-550 μM, respectively. To our knowledge this is the first report on the interaction of pharmaceutical compounds with enzymatic systems involved in the synthesis of oxy-androgens. As oxy-androgens are known to influence spermatogenesis and stimulate reproductive behavior and secondary sexual characteristics in male fish, this work highlights the need for further investigating these endpoints when designing specific in vivo studies to assess the endocrine disruptive effect of pharmaceuticals in fish.
authors.affiliation: Environmental Chemistry Department, IDAEA-CSIC, Jordi Girona 18, 08034 Barcelona, Spain. deniseferna@gmail.com
authors.forename: Denise
authors.initials: D
authors.lastname: Fernandes
authors.forename: Sabine
authors.initials: S
authors.lastname: Schnell
authors.forename: Cinta
authors.initials: C
authors.lastname: Porte
mesh_terms: D000728:Androgens / Q000378:metabolism*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000633:toxicity*; D000928:Antidepressive Agents / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism; D002347:Carps / Q000378:metabolism / Q000502:physiology*; D002994:Clofibrate / Q000633:toxicity; D002995:Clofibric Acid / Q000633:toxicity; D004008:Diclofenac / Q000633:toxicity; D058607:Fibric Acids / Q000633:toxicity*; D005473:Fluoxetine / Q000633:toxicity; D015248:Gemfibrozil / Q000633:toxicity; D007052:Ibuprofen / Q000633:toxicity; D008297:Male; D013252:Steroid 11-beta-Hydroxylase / Q000378:metabolism; D013254:Steroid 17-alpha-Hydroxylase / Q000378:metabolism; D013737:Testis / Q000378:metabolism; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D000728:Androgens; D000893:Anti-Inflammatory Agents; D000928:Antidepressive Agents; D015415:Biomarkers; D058607:Fibric Acids; D014874:Water Pollutants, Chemical; D005473:Fluoxetine; D004008:Diclofenac; D002995:Clofibric Acid; D013254:Steroid 17-alpha-Hydroxylase; D013252:Steroid 11-beta-Hydroxylase; D002994:Clofibrate; D015248:Gemfibrozil; D007052:Ibuprofen