邻苯二甲酸二丁酯对睾酮合成的影响

王玉邦; 宋玲; 朱正平; 陈建锋; 王心如

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

摘要

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。

Abstract:
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 sid-echain 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(HPTA)and local modulation in testis.

HTML全文

参考文献(5)

施引文献

资源附件(0)