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[邻苯二甲酸单(2-乙基己基)酯对大鼠睾丸培养的睾丸间质细胞睾酮生物合成的影响]

[Effects of mono(2-ethylhexyl) phthalate on testosterone biosynthesis in leydig cells cultured from the rat testis].

作者信息

Zhu Zheng-ping, Wang Yu-bang, Song Ling, Chen Jian-feng, Chang Hebron C, Wang Xin-ru

机构信息

Institute of Toxicology, Nanjing Medical University, Nanjing, Jiangsu 210029, China.

出版信息

Zhonghua Nan Ke Xue. 2005 Apr;11(4):247-51.

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 the Sprague Dawley rat testis.

METHODS

Based on the primary Leydig cell culture model, MEHP exposure groups involved control (0 micromol/L), 62.5, 125, 250, 500 and 1000 micromol/L. We observed mitochondria activity with the MTT method, measured the testosterone level with RIA and determined steroidogenesis acute regulatory protein (StAR) mRNA expression with RT-PCR.

RESULTS

After Leydig cells were exposed to MEHP for 24 hours, the activity of mitochondria enhanced evidently at 250 micromol/L and then declined markedly at 1000 micromol/L compared with the control group (P < 0.01). The testosterone level showed an increasing tendency in both basal and hCG-stimulated states with statistical significance at 250 and 500 micromol/L compared with the control group (P < 0.01). However, the expression of StAR mRNA appeared unchanged at 62.5, 125 or 250 micromol/L, but exhibited a decreasing tendency at 500 and 1000 micromol/L (P < 0.01).

CONCLUSION

ME- HP directly affected the activity of mitochondria and testosterone biosynthesis of the 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.

摘要

目的

研究邻苯二甲酸二(2-乙基己基)酯(DEHP)的主要代谢产物邻苯二甲酸单(2-乙基己基)酯(MEHP)对从Sprague Dawley大鼠睾丸培养的睾丸间质细胞睾酮生物合成的影响。

方法

基于原代睾丸间质细胞培养模型,MEHP暴露组包括对照组(0微摩尔/升)、62.5、125、250、500和1000微摩尔/升。我们用MTT法观察线粒体活性,用放射免疫分析法测定睾酮水平,用逆转录聚合酶链反应(RT-PCR)测定类固醇生成急性调节蛋白(StAR)mRNA表达。

结果

睾丸间质细胞暴露于MEHP 24小时后,与对照组相比,250微摩尔/升时线粒体活性明显增强,而在1000微摩尔/升时则明显下降(P<0.01)。在基础状态和人绒毛膜促性腺激素(hCG)刺激状态下,睾酮水平均呈上升趋势,与对照组相比,250和500微摩尔/升时具有统计学意义(P<0.01)。然而,在62.5、125或250微摩尔/升时,StAR mRNA表达未发生变化,但在500和1000微摩尔/升时呈下降趋势(P<0.01)。

结论

MEHP在体外直接影响睾丸间质细胞的线粒体活性和睾酮生物合成。StAR作为胆固醇转运至线粒体的调节因子,可能与MEHP诱导的睾酮生物合成增加无关。

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