Short period exposure to di-(2-ethylhexyl) phthalate regulates testosterone metabolism in testis of prepubertal rats
Short period exposure to di-(2-ethylhexyl) phthalate regulates testosterone metabolism in testis of prepubertal rats
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DOI：
10.1007/s00204-003-0466-7
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发表时间：
2003-06
影响因子：
6.1
通讯作者：
Hyung-Sub Kim;K. Saito;M. Ishizuka;A. Kazusaka;S. Fujita
中科院分区：
文献类型：
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作者：
Hyung-Sub Kim;K. Saito;M. Ishizuka;A. Kazusaka;S. Fujita
据报道，青春期大鼠暴露于邻苯二甲酸二（2-乙基己基）酯（DEHP）14天，通过改变雄烯二酮17β-羟基类固醇脱氢酶（17β-HSD）活性导致睾酮（T）生物合成减少。然而，我们的研究表明，4周龄雄性大鼠短期暴露于DEHP（100或1000 mg/kg，持续5天）不会影响睾丸中T生物合成的限速酶17β-HSD的活性。随着DEHP剂量的增加，睾丸中的T5 α-还原酶（T5α-R）活性显著增强，而芳香化酶mRNA显著降低。睾丸细胞色素P450（CYP）亚型CYP 2C 11和CYP 3A的表达沿着其酶活性T16α-和T6β-羟基化。因此，本研究清楚地表明，短期暴露于DEHP通过改变青春期前大鼠睾丸中T5α-R、芳香化酶和CYP 2C 11/3A 2的活性来改变T代谢，并且它们是对DEHP暴露更敏感的标记酶，而不是雄烯二酮的T生物合成酶。
Exposure of pubertal rats to di-(2-ethylhexyl) phthalate (DEHP) for 14 days was reported to result in reduced testosterone (T) biosynthesis by altering androstenedione 17β-hydroxysteroid dehydrogenase (17β-HSD) activity. However, our study indicated that shorter period exposure of DEHP (100 or 1000 mg/kg for 5 days) to 4-week-old male rats did not affect the activity of 17β-HSD, the rate-limiting enzyme of T biosynthesis in the testis. Testosterone 5α-reductase (T5α-R) activity in the testis was significantly enhanced, while aromatase mRNA was significantly reduced by increasing doses of DEHP. The expressions of cytochrome P450 (CYP) isoforms, CYP2C11 and CYP3A, in the testis increased along with their enzymatic activities, T16α- and T6β-hydroxylation, respectively. Thus, the current study clearly indicates that the short period exposure to DEHP alters T metabolism through altering activities of T5α-R, aromatase and CYP2C11/3A2 in the testis of prepubertal rats, and that they are more sensitive marker enzymes to the DEHP exposure than those of biosynthetic enzymes of T from androstenedione.