【作者】 朱正平； 王玉邦； 宋玲； 陈建锋； 张淳文； 王心如；

【Author】 Zhu Zheng-ping, Wang Yu-bang, Song Ling, Chen Jian-feng, Chang Hebron C, Wang Xin-ru (Institute of Toxicology, Nanjing Medical University, Jiangsu, Nanjing 210029 China), (Zhu ZP, Wang YB, Song L, Chen JF, Chang HC, Wang XR)

【机构】 南京医科大学毒理学研究所；

【摘要】 [目的]探讨邻苯二甲酸二乙基己基酯(DEHP)的代谢产物邻苯二甲酸单乙基己基酯(MEHP)对SD大鼠体外培养睾丸间质细胞(Leydig cells)睾酮合成的影响。[方法]建立SD大鼠睾丸Leydig细胞体外原代培养模型,MEHP染毒剂量组分为对照(0μmol/L)、62.5、125、250、500和1000μmol/L,通过噻唑蓝(MTT)法观察线粒体活性,放射免疫法测定睾酮浓度、RT-PCR法测定Leydig细胞类固醇合成急性调节蛋白(StAR)mRNA表达。[结果]MEHP染毒24h后,Leydig细胞线粒体活性在250μmol/L显著上升,在1000μmol/L显著下降,与对照组比较,均有差异显著性(P<0.01)。基础状态及hCG刺激状态下,Leydig细胞睾酮合成水平均呈上升趋势,与对照组相比,250、500μmol/L剂量组差异均有显著性(P<0.01)。Leydig细胞StAR mRNA的表达在62.5、125、250μmol/L时与对照组相比均未见有显著性改变,在500、1000μmol/L时显著下降(P<0.01)。[结论] MEHP直接影响原代培养Leydig细胞线粒体活性及睾酮合成,胆固醇跨膜转运的调节因子StAR与MEHP引起睾酮合成上升的原因可能无关。更多还原

【Abstract】 [Objective] To investigate the effects of mono(2-ethylhexyl)phthalate(MEHP), the primary metabolite of di(2-ethylhexyl)phthalate(DEHP), on testosterone biosynthesis in Leydig cells cultured from Sprague Dawley rat testis. [Methods] Based on the primary Leydig cell culture model, MEHP exposure groups involved control (0μmol/L), 62.5, 125,250, 500 and 1000μmol/L. We observed mitochondria activity with MTT method, measured testosterone level with RIA and determined steroidogenesis acute regulatory protein (StAR) mRNA expression with RT-PCR. [Results] After Leydig cells exposed to MEHP for 24 hours, the activity of mitochondria enhanced evidently at 250μmol/L then declined markedly at 1000μmol/L compared with the control group (P<0.01). Testosterone level showed an increasing tendency at both basal and hCG-stimulated states with statistical significances at 250 and 500μmol/L compared with the control group (P<0.01), however, the expression of StAR mRNA appeared unchanged at 62.5,125 or 250μmol/L, but exhibited a decrease tendency at 500 and 1000μmol/L(P<0.01). [Conclusion] MEHP directly affected the activity of mitochondria and testosterone biosynthesis of Leydig cells in vitro. StAR, the regulator of cholesterol transport into mitochondria, might not be responsible for the increase of testosterone biosynthesis induced by MEHP.更多还原