Inhibition of 3beta- and 17beta-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 3beta-hydroxysteroid dehydrogenase (3beta-HSD) and 17beta-hydroxysteroid dehydrogenase 3 (17beta-HSD3) activities in rat testis microsomes and Leydig cells. The IC(50)s of PFOA and mode of inhibition were assayed. PFOA inhibited microsomal 3beta-HSD with an IC(50) of 53.2+/-25.9 microM and 17beta-HSD3 with an IC(50) 17.7+/-6.8 microM. PFOA inhibited intact Leydig cell 3beta-HSD with an IC(50) of 146.1+/-0.9 microM and 17beta-HSD3 with an IC(50) of 194.8+/-1.0 microM. The inhibitions of 3beta-HSD and 17beta-HSD3 by PFOA were competitive for the substrates. In conclusion, PFOA inhibits 3beta-HSD and 17beta-HSD3 in rat Leydig cells.
Zhao
Binghai
B
School of Public Health, Jilin University, Changchun, Jilin, People's Republic of China.
Chu
Yanhui
Y
Hardy
Dianne O
DO
Li
Xiao-kun
XK
Ge
Ren-Shan
RS
D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015096:3-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D055162:Biocatalysis; D002210:Caprylates / Q000494:pharmacology*; D002478:Cells, Cultured; D004785:Environmental Pollutants / Q000009:adverse effects / Q000494:pharmacology; D005466:Fluorocarbons / Q000494:pharmacology*; D007700:Kinetics; D007985:Leydig Cells / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D007986:Luteinizing Hormone / Q000494:pharmacology; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013737:Testis / Q000201:enzymology; D013739:Testosterone / Q000378:metabolism
D002210:Caprylates; D004785:Environmental Pollutants; D005466:Fluorocarbons; D013739:Testosterone; D007986:Luteinizing Hormone; C023036:perfluorooctanoic acid; D015067:17-Hydroxysteroid Dehydrogenases; C476565:17beta-hydroxysteroid dehydrogenase type 3; D015096:3-Hydroxysteroid Dehydrogenases