邻苯二甲酸二丁酯对睾酮合成的影响  

Effects of dibutyl phthalate on testosterone biosynthesis in rats

作　　者：王玉邦 宋玲[1] 朱正平[1] 陈建锋[1] 王心如[1] 

机构地区：[1]南京医科大学毒理学研究所,南京210029

出　　处：《中国公共卫生》2005年第10期1168-1170,共3页Chinese Journal of Public Health

基　　金：国家重点基础研究发展规划资助(国家973项目2002CB512908)

摘　　要：目的探讨邻苯二甲酸二丁酯(DBP)对睾酮合成的影响及相关机制。方法6周龄雄性SD大鼠随机分成0,250,500和1 000 mg/(kg.d)4组,每组8只,灌胃给予DBP。放免法测定黄体生成素(LH)、17β雌二醇(17βE2)、睾酮(T)。RT-PCR法测定细胞色素P450胆固醇侧链裂解酶(P450scc)mRNA和3β类固醇脱氢酶(3βHSD)mRNA的相对表达量。结果血清17βE2浓度在DBP250和1 000 mg/(kg.d)剂量组与对照组比较差异有统计学意义(P<0.01)。血清和匀浆T浓度500和1 000 mg/(kg.d)剂量组与对照组比较差异均有统计学意义(P<0.01)。P450scc mRNA和3βHSDmRNA表达水平随着染毒剂量的增加下降趋势明显。相关与回归分析结果显示,mRNA(Y)表达水平与染毒剂量(对数,X)之间存在明显的剂量-依赖关系,P450scc mRNA:r=0.78,Y=0.54-0.10X(P<0.01);3βHSD mRNA:r=0.79,Y=0.79-0.13X(P<0.01)。结论间质细胞是DBP的主要靶细胞之一。DBP导致T合成减少的可能机制包括T合成相关酶mRNA表达水平的下调和17βE2水平的上升干扰了下丘脑-垂体-睾丸轴的生理平衡。Objective To investigate the effects of dibutyl phthalate（DBP）on testosterone biosynthesis and its related mechanism in rats. Methods Six-week-old healthy male SD rats were randomly divided into 4 groups with 8 animals per group. DBP dissolved in peanut oil was administered by gavage at doses of 0,250,500, 1 000 mg/（kg·d）. After 4-week DBP exposure, the animals were sacrificel with testis selected and weighed, Luteinizing hormone （LH）, 17β estradiol（ 17β-E2 ）, testosterone（T）were detected by radioimmunoassay. The relative expression levels of cholesterol side-chain cleavage enzyme （P450scc）mRNA and 3beta-hydroxysteroid dehydrogenase（3β-HSD）mRNA were determined by RT-PCR. Results LH levels in serum were not significantly changed, whereas 17βE2 in serum elevated noticeably induced by DBP. T levels in testis homogenate and in serum reduced signifcantly in 500 and 1 000 mg/（kg · d）groups. Furthermore, mRNA expression was downregulated for P450scc and 3β-HSD following DBP exposure. Linear correlation and regression revealed that there were obvious relationships between dosages（logarithm） and the expression of P450scc mRNA and 3β-HSD mRNA. Conclusion Leydig cells may be one of the major target cell affected by DBP. It is likely that downregulation of T biosynthetic enzymes mRNA may be key factors contributing to the decrease of T concentration. Secondly, The increase of 17βE2 disordered physiologic balances of hypothalamic-pituitary-testis axis（HPmA）and local modulation in testis.

关 键 词：邻苯二甲酸二丁酯 大鼠 睾丸 睾酮 

分 类 号：R994.6[医药卫生—毒理学]