【作者】 王玉邦； 宋玲； 朱正平； 陈建锋； 王心如；

【Author】 WANG Yu-bang, SONG Ling, ZHU Zheng-ping, et al. Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China

【机构】 南京医科大学毒理学研究所；

【摘要】 [目的]探讨邻苯二甲酸二丁酯(DBP)对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1000 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DBP 250 mg/(kg·d)和1 000 mg/(kg·d)剂量组与对照组比较差异有显著性(P<0.01)。血清和匀浆T浓度500 mg/(kg·d)和1000 mg/(kg·d)剂量组与对照组比较差异均有显著性(P<0.01)。P450scc mRNA和3β-HSD mRNA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-依赖反应关系,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、17βE2水平的上升干扰了下丘脑-垂体一睾丸轴的生理平衡。更多还原

【Abstract】 [Objective] To investigate the effects of dibutyl phthalate (DBF) 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, 500,1000 mg/(kg·d). After 4-week DBP exposure, the animals were sacrificed with testis selected and weighed. Luteinizing hormone ( LH), 17βestradiol(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 significantly in 500 and 1000 mg/(kgβd) groups. Furthermore, mRNA expression was downregulated for P450scc and 3P-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 might 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(HPTA) and local modulation in testis.更多还原