Mice lacking Mrp1 have reduced testicular steroid hormone levels and alterations in steroid biosynthetic enzymes.
Mice lacking Mrp1 have reduced testicular steroid hormone levels and alterations in steroid biosynthetic enzymes.
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DOI：
10.1016/j.ygcen.2010.02.019
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发表时间：
2010-05-15
影响因子：
2.7
通讯作者：
Bain, Lisa J.
中科院分区：
文献类型：
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作者：
Sivils, Jeffrey C.;Gonzalez, Iven;Bain, Lisa J.
关键词：
多药耐药相关蛋白1（MRP1/ABCC1）是ABC活性转运蛋白家族的成员，可转运多种类固醇激素结合物，包括17 β-雌二醇葡萄糖醛酸苷、硫酸脱氢表雄酮（DHEAS）和3-硫酸雌酮。本研究调查了MRP 1在维持血清和睾丸中适当激素水平方面所发挥的作用。在野生型小鼠和Mrp1基因敲除小鼠中检查血清和睾丸类固醇激素水平。血清睾酮水平在缺乏Mrp1的小鼠中降低了5倍，而睾丸雄烯二酮，睾酮，雌二醇和脱氢表雄酮（DHEA）在Mrp1敲除小鼠中显著降低了1.7至4.5倍。调查负责减少类固醇激素在Mrp1-/-小鼠的机制显示没有差异的表达或活性的酶，类固醇，磺基转移酶或葡萄糖醛酸基转移酶。然而，睾丸中的类固醇生物合成酶水平发生了变化。Cyp17蛋白水平增加了1.6倍，而在缺乏Mrp1的小鼠中，使用孕酮作为底物的Cyp17活性也增加了1.4 - 2.0倍。此外，17 β-羟基类固醇脱氢酶与3 β-羟基类固醇脱氢酶的比率以及类固醇生成因子1与3 β-羟基类固醇脱氢酶的比率在Mrp 1-/-小鼠的睾丸中显著增加。这些结果表明，Mrp1-/-小鼠降低了类固醇激素水平，并表明类固醇生物合成酶的上调可能是试图维持适当的类固醇激素稳态。
The multidrug resistance-associated protein 1 (MRP1/ABCC1) is a member of the ABC active transporter family that can transport several steroid hormone conjugates, including 17β-estradiol glucuronide, dehydroepiandrosterone sulfate (DHEAS), and estrone 3-sulfate. The present study investigated the role that MRP1 plays in maintaining proper hormone levels in the serum and testes. Serum and testicular steroid hormone levels were examined in both wild-type mice and Mrp1 null mice. Serum testosterone levels were reduced 5-fold in mice lacking Mrp1, while testicular androstenedione, testosterone, estradiol, and dehydroepiandrosterone (DHEA) were significantly reduced by 1.7- to 4.5-fold in Mrp1 knockout mice. Investigating the mechanisms responsible for the reduction in steroid hormones in Mrp1-/- mice revealed no differences in the expression or activity of enzymes that inactivate steroids, the sulfotransferases or glucuronosyltransferases. However, steroid biosynthetic enzyme levels in the testes were altered. Cyp17 protein levels were increased by 1.6-fold, while Cyp17 activity using progesterone as a substrate was also increased by 1.4-2.0-fold in mice lacking Mrp1. Additionally, the ratio of 17β-hydroxysteroid dehydrogenase to 3β-hydroxysteroid dehydrogenase, and steroidogenic factor 1 to 3βhydroxysteroid dehydrogenase were significantly increased in the testes of Mrp1-/- mice. These results indicate that Mrp1-/- mice have lowered steroid hormones levels, and suggests that upregulation of steroid biosynthetic enzymes may be an attempt to maintain proper steroid hormone homeostasis.
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影响因子：
3.8
作者：
Harini, C.;Sainath, S. B.;Reddy, P. Sreenivasula
通讯作者：
Reddy, P. Sreenivasula
影响因子：
3.3
作者：
Nies, AT;Jedlitschky, G;Keppler, D
通讯作者：
Keppler, D
影响因子：
3.7
作者：
Li, Q;Kato, Y;Tsuji, A
通讯作者：
Tsuji, A
影响因子：
2.8
作者：
Busygina, TV;Vasiliev, GV;Osadchuk, AV
通讯作者：
Osadchuk, AV
DOI：
10.1186/1477-7827-3-51
发表时间：
2005-09-27
期刊：
Reproductive biology and endocrinology : RB&E
影响因子：
--
作者：
Akingbemi BT
通讯作者：
Akingbemi BT