Roundup inhibits steroidogenesis by disrupting steroidogenic acute regulatory (StAR) protein expression.
Roundup inhibits steroidogenesis by disrupting steroidogenic acute regulatory (StAR) protein expression.
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DOI：
10.1289/ehp.00108769
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发表时间：
2000-08
影响因子：
10.4
通讯作者：
Stocco DM
中科院分区：
文献类型：
--
作者：
Walsh LP;McCormick C;Martin C;Stocco DM
最近的报告表明，目前使用的许多农药都有能力破坏动物的生殖功能。尽管这种生殖功能障碍的典型特征是血清类固醇激素水平的改变、精子发生的破坏和生育能力的丧失，但农药引起的不育的机制仍不清楚。由于睾丸间质细胞通过产生睾酮在男性生殖功能中发挥着至关重要的作用，因此我们使用小鼠 MA-10 间质肿瘤细胞系来研究农药诱导的类固醇激素生物合成改变所涉及的分子事件。我们之前表明，有机氯杀虫剂林丹和有机磷杀虫剂乐果通过破坏类固醇生成急性调节（StAR）蛋白的表达，直接抑制 Leydig 细胞中的类固醇生成。 StAR 蛋白介导类固醇生成中的限速和急性调节步骤，即胆固醇从线粒体外膜转移到线粒体内膜，其中细胞色素 P450 侧链裂解 (P450scc) 酶启动所有类固醇激素的合成。在本研究中，我们筛选了目前使用的八种农药制剂抑制类固醇生成的能力，重点研究它们对 MA-10 细胞中 StAR 表达的影响。此外，我们还确定了这些化合物对 P450scc 酶（将胆固醇转化为孕烯醇酮）和 3β-羟基类固醇脱氢酶 (3β-HSD)（将孕烯醇酮转化为黄体酮）的水平和活性的影响。在筛选的农药中，只有农达农药能抑制 MA-10 细胞中二丁酰 [(Bu)(2)]cAMP 刺激的孕酮产生，且不会引起细胞毒性。农达通过破坏 StAR 蛋白表达来抑制类固醇生成，进一步证明了 StAR 对环境污染物的敏感性。
Recent reports demonstrate that many currently used pesticides have the capacity to disrupt reproductive function in animals. Although this reproductive dysfunction is typically characterized by alterations in serum steroid hormone levels, disruptions in spermatogenesis, and loss of fertility, the mechanisms involved in pesticide-induced infertility remain unclear. Because testicular Leydig cells play a crucial role in male reproductive function by producing testosterone, we used the mouse MA-10 Leydig tumor cell line to study the molecular events involved in pesticide-induced alterations in steroid hormone biosynthesis. We previously showed that the organochlorine insecticide lindane and the organophosphate insecticide Dimethoate directly inhibit steroidogenesis in Leydig cells by disrupting expression of the steroidogenic acute regulatory (StAR) protein. StAR protein mediates the rate-limiting and acutely regulated step in steroidogenesis, the transfer of cholesterol from the outer to the inner mitochondrial membrane where the cytochrome P450 side chain cleavage (P450scc) enzyme initiates the synthesis of all steroid hormones. In the present study, we screened eight currently used pesticide formulations for their ability to inhibit steroidogenesis, concentrating on their effects on StAR expression in MA-10 cells. In addition, we determined the effects of these compounds on the levels and activities of the P450scc enzyme (which converts cholesterol to pregnenolone) and the 3beta-hydroxysteroid dehydrogenase (3beta-HSD) enzyme (which converts pregnenolone to progesterone). Of the pesticides screened, only the pesticide Roundup inhibited dibutyryl [(Bu)(2)]cAMP-stimulated progesterone production in MA-10 cells without causing cellular toxicity. Roundup inhibited steroidogenesis by disrupting StAR protein expression, further demonstrating the susceptibility of StAR to environmental pollutants.
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DOI：
10.1073/pnas.94.21.11540
发表时间：
1997-10-14
影响因子：
11.1
作者：
Caron, KM;Soo, SC;Parker, KL
通讯作者：
Parker, KL
影响因子：
--
作者：
NOLAN, CJ;PAYNE, AH
通讯作者：
PAYNE, AH
影响因子：
3.8
作者：
RYBCZYNSKI, R;GILBERT, LI
通讯作者：
GILBERT, LI
影响因子：
3.6
作者：
Fiedler, EP;Plouffe, L;Khan, I
通讯作者：
Khan, I
DOI：
10.1016/s0960-0760(98)00153-8
发表时间：
1999-04-01
影响因子：
4.1
作者：
Miller, WL;Strauss, JF
通讯作者：
Strauss, JF