首页> 外文OA文献 >Inhibition of hormone-stimulated steroidogenesis in cultured Leydig tumor cells by a cholesterol-linked phosphorothioate oligodeoxynucleotide antisense to diazepam-binding inhibitor.
【2h】

Inhibition of hormone-stimulated steroidogenesis in cultured Leydig tumor cells by a cholesterol-linked phosphorothioate oligodeoxynucleotide antisense to diazepam-binding inhibitor.

机译:胆固醇连接的硫代磷酸酯寡脱氧核苷酸对地西epa结合抑制剂的反义抑制在培养的Leydig肿瘤细胞中激素刺激的类固醇生成的抑制作用。

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务,本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文,但由于OA文献来源多样且变更频繁,仍可能出现获取不到、文献不完整或与标题不符等情况,如果获取不到我们将提供退款服务。请知悉。

摘要

The polypeptide diazepam-binding inhibitor (DBI) has been previously shown to stimulate testicular Leydig, adrenocortical, and glial-cell mitochondrial steroidogenesis in vitro. To assess the in situ role of DBI in trophic hormone-stimulated steroidogenesis, we suppressed DBI levels in the hormone-responsive MA-10 Leydig tumor cells, using a cholesterol-linked phosphorothioate oligodeoxynucleotide (Chol-odN) antisense to DBI. Treating MA-10 cells with Chol-odN antisense to DBI resulted in a dose-dependent reduction of DBI levels (ED50 = 1 microM). In contrast, Chol-odN sense to DBI did not affect its expression. Saturating amounts of human choriogonadotropin (hCG) increased MA-10 progesterone production by 150-fold. Addition of increased concentrations of Chol-odNs sense to DBI or of a nonrelated sequence did not reduce the MA-10 response to hCG. However, in the presence of Chol-odN antisense to DBI that could reduce DBI levels, MA-10 cells lost their ability to respond to hCG (ED50 = 1 microM). In these studies the hCG-stimulated cAMP levels and cytochrome P450 side-chain cleavage activity, as measured by metabolism of 22(R)-hydroxycholesterol, were not affected by the Chol-odNs used. These observations provide unequivocal evidence that DBI plays a vital role in the acute stimulation of steroidogenesis by trophic hormones.
机译:先前已证明多肽地西epa结合抑制剂(DBI)在体外刺激睾丸Leydig,肾上腺皮质和神经胶质细胞线粒体的类固醇生成。为了评估DBI在营养激素刺激的类固醇生成中的原位作用,我们使用了胆固醇相关的硫代磷酸酯寡聚脱氧核苷酸(Chol-odN)反义物,抑制了激素反应性MA-10 Leydig肿瘤细胞中的DBI水平。用针对DBI的Chol-odN反义物处理MA-10细胞导致剂量依赖性DBI水平降低(ED50 = 1 microM)。相反,对DBI的Chol-odN感觉并没有影响其表达。饱和人绒毛膜促性腺激素(hCG)的量可使MA-10孕酮的产量增加150倍。向DBI或无关序列中增加Chol-odNs感官浓度的浓度不会降低MA-10对hCG的反应。但是,在存在可降低DBI水平的针对DBI的Chol-odN反义分子的情况下,MA-10细胞丧失了对hCG的反应能力(ED50 = 1 microM)。在这些研究中,通过22(R)-羟基胆固醇代谢测定的hCG刺激的cAMP水平和细胞色素P450侧链裂解活性不受所用Chol-odNs的影响。这些观察结果明确表明,DBI在营养激素对类固醇的急性刺激中起着至关重要的作用。

著录项

相似文献

  • 外文文献
  • 专利
代理获取

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号