Can pharmaceuticals interfere with the synthesis of active androgens in male fish? An in vitro study

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.