Inhibition of 3 beta- and 17 beta-hydroxysteroid dehydrogenase activities in rat Leydig cells by perfluorooctane acid

Perfluorooctane acid (PFOA) is classified as a persistent organic pollutant and as an endocrine disruptor. The mechanism by which PFOA causes reduced testosterone production in males is not known. We tested our hypothesis that PFOA interferes with Leydig cell steroiclogenic enzymes by measuring its effect on 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and 17 beta-hydroxysteroid dehydrogenase 3 (17 beta-HSD3) activities in rat testis microsomes and Leydig cells. The IC(50)s of PFOA and mode of inhibition were assayed. PFOA inhibited microsomal 3 beta-HSD with an IC50 of 53.2 +/- 25.9 mu M and 17 beta-HSD3 with an IC50 17.7 +/- 6.8 mu M. PFOA inhibited intact Leydig cell 3 beta-HSD with an IC50 of 146.1 +/- 0.9 mu M and 17 beta-HSD3 with an IC50 of 194.8 +/- 1.0 mu M. The inhibitions of 3 beta-HSD and 17 beta-HSD3 by PFOA were competitive for the substrates. In conclusion, PFOA inhibits 3 beta-HSD and 17 beta-HSD3 in rat Leydig cells. (C) 2009 Elsevier Ltd. All rights reserved.