Inhibition of 3β- and 17β-hydroxysteroid dehydrogenase activities in rat Leydig cells by perfluorooctane acid
Inhibition of 3β- and 17β-hydroxysteroid dehydrogenase activities in rat Leydig cells by perfluorooctane acid
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DOI：
10.1016/j.jsbmb.2009.09.010
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发表时间：
2010-01
期刊：
影响因子：
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通讯作者：
Binghai Zhao;Y. Chu;D. Hardy;Xiao-kun Li;R. Ge
中科院分区：
文献类型：
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作者：
Binghai Zhao;Y. Chu;D. Hardy;Xiao-kun Li;R. Ge
全氟辛烷酸被列为持久性有机污染物和内分泌干扰物。PFOA导致男性睾酮分泌减少的机制尚不清楚。我们通过测量PFOA对大鼠睾丸微粒体和Leydig细胞中3β-羟基类固醇脱氢酶（3β-HSD）和17β-羟基类固醇脱氢酶3（17β-HSD 3）活性的影响，验证了我们的假设，即PFOA干扰Leydig细胞类固醇生成酶。测定了PFOA的IC_（50）和抑制模式。PFOA抑制微粒体3β-HSD的IC 50为53.2±25.9μM，抑制17β-HSD 3的IC 50为17.7 ±6.8μM。PFOA抑制睾丸间质细胞3β-HSD和17β-HSD 3的IC 50分别为146.1±0.9μM和194.8±1.0μM。PFOA对3β-HSD和17β-HSD 3的抑制作用与底物之间存在竞争性。总之，PFOA抑制大鼠Leydig细胞中的3β-HSD和17β-HSD 3。
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 IC50of 53.2±25.9μM and 17β-HSD3 with an IC5017.7±6.8μM. PFOA inhibited intact Leydig cell 3β-HSD with an IC50of 146.1±0.9μM and 17β-HSD3 with an IC50of 194.8±1.0μM. 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.