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首页> 外文期刊>Life sciences >Suppression of fetal testicular cytochrome P450 17 by maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin: a mechanism involving an initial effect on gonadotropin synthesis in the pituitary.
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Suppression of fetal testicular cytochrome P450 17 by maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin: a mechanism involving an initial effect on gonadotropin synthesis in the pituitary.

机译：孕妇暴露于2,3,7,8-四氯二苯并-p-二恶英可抑制胎儿睾丸细胞色素P450 17：一种机制涉及垂体促性腺激素合成的初步作用。

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摘要

The effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on the fetal expression of testicular cytochrome P450 17 (CYP17), one of the enzymes necessary for sex steroid synthesis, was studied in Wistar rats. Fetal testicular CYP17 exhibited reduced mRNA and protein levels following exposure of the dams at gestational day 15 to 1 microg/kg TCDD. In support of this, CYP17 activity catalyzed by fetal testis homogenate was also reduced by maternal exposure to TCDD. The reduction in CYP17 expression seemed to be specific for fetal stages, because 7 day-old pups born from TCDD-treated dams did not exhibit any reduction in CYP17. In sharp contrast to the in vivo observations, TCDD failed to reduce CYP17 expression in cultured fetal testis, although CYP17 could be induced by activating cAMP-dependent signaling. To assess the role of pituitary luteinizing hormone (LH) on TCDD-induced reduction in fetal testicular CYP17, a further investigation was performed to examine whether the direct injection of LH into fetuses restores the altered CYP17 expression. The results showed that in utero injection of equine chorionic gonadotropin, an LH-mimicking hormone, completely abolishes the TCDD-produced reduction in fetal CYP17. However, neither the alpha- nor beta-subunits of LH in cultured fetal pituitary was reduced by TCDD. These results suggest that 1) maternal exposure to TCDD impairs the expression of testicular CYP17 in a fetal stage-specific manner; 2) this effect is due, at least partially, to a TCDD-produced reduction in circulating LH; and 3) TCDD exerts such an effect by affecting the upstream mechanism regulating the pituitary synthesis of LH.
机译：在Wistar大鼠中研究了2,3,7,8-四氯二苯并-对-二恶英（TCDD）对胎儿睾丸细胞色素P450 17（CYP17）表达的影响，CYP17是性类固醇合成所必需的酶之一。胎儿睾丸CYP17在妊娠第15天暴露于大坝至1 microg / kg TCDD后表现出降低的mRNA和蛋白质水平。为此，孕妇暴露于TCDD也会降低胎儿睾丸匀浆催化的CYP17活性。 CYP17表达的减少似乎对胎儿阶段是特定的，因为由TCDD处理的母鼠出生的7日龄幼崽并未表现出CYP17的任何减少。与体内观察结果形成鲜明对比的是，尽管可通过激活cAMP依赖性信号传导来诱导CYP17，但TCDD未能降低培养的胎儿睾丸中CYP17的表达。为了评估垂体促黄体生成激素（LH）在TCDD诱导的胎儿睾丸CYP17减少中的作用，进行了进一步的研究，以检查将LH直接注入胎儿是否能恢复改变的CYP17表达。结果表明，在子宫内注射马绒毛膜促性腺激素（一种模仿LH的激素）完全消除了TCDD引起的胎儿CYP17降低。但是，TCDD不能降低培养的胎儿垂体中LH的α-亚基和β-亚基。这些结果表明：1）母体暴露于TCDD会以胎儿期特异性方式损害睾丸CYP17的表达; 2）这种影响至少部分是由于TCDD产生的循环LH减少所致; 3）TCDD通过影响调节LH垂体合成的上游机制发挥这种作用。

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