双酚A对大鼠未成年Leydig细胞睾酮合成的影响及机制

摘要

Objective To observe the effects of bisphenol A on testosterone( T) biosynthesis in rat immature Leydig cells, and to explore the protein expression of glucocorticoid receptor( CR) , 11β - hydroxysteroid dehydrogenage( 11β - HSD) and steroidogenic acute regulatory protein ( StAR) . Methods 24 Sprague - Dawley weaning rats were divided randomly into four groups : normal control group(n = 6) ,low dose of BPA group( n = 6) , middle dose of BPA group( n = 6) , high dose of BPA group( n = 6) . Rats in the latter three groups received BPA at the dosage of 2.4μg,1mg and 200mg/kg respectively per day by gavage from post - natalday 21to 35. Rats in the narmal control group received corn oil at the same volume. The morphologic changes of Leydig cells were observed under light microscopy microscopy ( LM ) and transmission electron microscopy ( TEM ) respectively. Serum testosterone was measured by ELISA. The protein expression of GR,11β - HSD and SiAR in the testicular Leydig cells was measured hy Westem blotting. Results Obvious mitochrondria expansion of Leydig cells was observed in the high dose group. Decrease of serum T was detected in the low dose group . The protein expression of GR increased in low dose group and decreased in middle and high dose groups. The protein expressions of 11 β - HSD and StAR deereased in high dose group. Conclusion Bisphenol A can affect T biosynthesis in rat immature Leydig cells. Change of protein expression of GR,11β - HSD and StAR may be involved in.%目的 观察双酚A(bisphenol A,BPA)对大鼠未成年Leydig细胞睾酮合成的影响,探讨糖皮质激素受体(GR)、11β羟类固醇脱氢酶(11β-HSD)及类固醇激素合成急性调节蛋白(StAR)蛋白表达的改变及意义.方法 雄性SD大鼠24只,随机均分成4组:正常对照组、低剂量组、中剂量组、高剂量组.低剂量组、中剂量组及高剂量组予出生后第21天起分别给予不同剂量[(2.4μg/(kg·d)、1mg/(kg·d)、200mg/(kg·d)]的双酚A灌胃至出生后第35天.正常对照组给予等容积的玉米油灌胃.实验结束时处死大鼠, 测量大鼠体重、睾丸重量,光镜及电镜下观察睾丸Leydig细胞的形态学改变,酶联免疫吸附测定法检测血清睾酮浓度,Western-blotting法检测睾丸Leydig细胞GR、11β-HSD及StAR的蛋白表达.结果 高剂量组Leydig细胞线粒体肿胀明显.低剂量组大鼠血清睾酮下降(P<0.05) .低剂量组大鼠睾丸Leydig细胞GR蛋白表达升高(P<0.05),中剂量和高剂量组大鼠睾丸Leydig细胞GR蛋白表达明显降低(P<0.01), 高剂量组大鼠睾丸Leydig细胞11β-HSD蛋白及StAR蛋白表达降低(P<0.05).结论 双酚A可以干扰大鼠未成年Leydig细胞的睾酮合成,GR、11β-HSD及StAR的蛋白表达改变可能是其重要机制.