Inhibition of 3β- and 17β-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 steroidogenic enzymes by measuring its effect on 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-hydroxysteroid dehydrogenase 3 (17β-HSD3) activities in rat testis microsomes and Leydig cells. The IC50s of PFOA and mode of inhibition were assayed. PFOA inhibited microsomal 3β-HSD with an IC50 of 53.2 ± 25.9 μM and 17β-HSD3 with an IC50 17.7 ± 6.8 μM. PFOA inhibited intact Leydig cell 3β-HSD with an IC50 of 146.1 ± 0.9 μM and 17β-HSD3 with an IC50 of 194.8 ± 1.0 μM. The inhibitions of 3β-HSD and 17β-HSD3 by PFOA were competitive for the substrates. In conclusion, PFOA inhibits 3β-HSD and 17β-HSD3 in rat Leydig cells.