Inhibition of human and rat 3β-hydroxysteroid dehydrogenase and 17β-hydroxysteroid dehydrogenase 3 activities by perfluoroalkylated substances

Perfluoroalkylated substances (PFASs) including perfluorooctane acid (PFOA) and perfluorooctane sulfonate (PFOS) have been classified as persistent organic pollutants and are known to cause reduced testosterone production in human males. The objective of the present study was to compare the potencies of five different PFASs including PFOA. PFOS, potassium perfluorooctane sulfonate (PFOSK), potassium perfluorohexane sulfonate (PFHxSK) and potassium perfluorobutane sulfonate (PFBSK) in the inhibition of 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) and 17 beta-hydroxysteroid dehydrogenase 3 (17 beta-HSD3) activities in the human and rat testes. Human and rat microsomal enzymes were exposed to various PFASs. PFOS and PFOSK inhibited rat 3 beta-HSD activity with IC50 of 1.3.5 +/- 0.05 and 1.77 +/- 0.04 mu M, respectively, whereas PFHxSK and PFBSK had no effect at concentrations up to 250 mu M. All chemicals tested weakly inhibited human 3 beta-HSD activity with IC(50)s over 250 mu M. On the other hand, PFOS. PFOSK and PFOA inhibited human 17 beta-HSD3 activity with IC(50)s of 6.02 +/- 1.02, 4.39 +/- 0.46 and 127.60 +/- 28.52 mu M, respectively. The potencies for inhibition of 17 beta-HSD3 activity were determined to be PFOSK > PFOS> PFOA> PFHxSK = PFBSK for human 17 beta-HSD3 activity. There appears to be a species-dependent sensitivity to PFAS-mediated inhibition of enzyme activity because the IC(50)s of PFOS(K) for inhibition of rat 17 beta-HSD3 activity was greater than 250 mu M. In conclusion, the present study shows that PFOS and PFOSK are potent inhibitors of rat 3 beta-HSD and human 17 beta-HSD3 activity, and implies that inhibition of steroidogenic enzyme activity may be a contributing factor to the effects that PFASs exert on androgen secretion in the testis. (C) 2010 Elsevier Ireland Ltd. All rights reserved.