The Transcriptional Factor Prolactin Regulatory Element-Binding Protein Mediates the Gene Transcription of Adrenal Scavenger Receptor Class B Type I via 3′,5′-Cyclic Adenosine 5′-Monophosphate
The Transcriptional Factor Prolactin Regulatory Element-Binding Protein Mediates the Gene Transcription of Adrenal Scavenger Receptor Class B Type I via 3′,5′-Cyclic Adenosine 5′-Monophosphate
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DOI：
10.1210/en.2008-0380
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发表时间：
2008-12-01
期刊：
影响因子：
4.8
通讯作者：
Ishida, Toshihiko
中科院分区：
文献类型：
--
作者：
Murao, Koji;Imachi, Hitomi;Ishida, Toshihiko
催乳素调节元件结合蛋白（PREB）是调节大鼠垂体前叶催乳素启动子活性的转录因子。PREB蛋白不仅在垂体前叶中表达，而且在肾上腺中也表达。然而，PREB在肾上腺中的作用尚不清楚。I型B类清道夫受体（SR-BI）是介导细胞摄取高密度脂蛋白胆固醇酯的高密度脂蛋白受体，并且是胆固醇递送至肾上腺中类固醇生成途径的主要途径。在本研究中，我们研究了PREB在调节SR-BI中的作用。SR-BI的表达受cAMP的调节，cAMP以剂量依赖的方式刺激PREB的表达。相反，使用表达PREB的腺病毒过表达PREB增加了肾上腺皮质细胞系Y-1中SR-BI蛋白的表达。此外，PREB诱导SR-BI启动子控制下的荧光素酶报告蛋白的表达。EMSA表明PREB通过与SR-BI启动子的PREB应答顺式元件结合来介导其转录效应。最后，我们使用小干扰RNA来抑制Y-1细胞中的PREB表达，并证明PREB表达的敲低减弱了cAMP对SR-BI表达的影响。总之，我们的数据表明，在肾上腺中，PREB通过cAMP调节SR-BI基因的转录。（内分泌学149：6103-6112，2008）
Prolactin regulatory element-binding ( PREB) protein is a transcription factor that regulates prolactin promoter activity in the rat anterior pituitary. The PREB protein is not only expressed in the anterior pituitary but also in the adrenal gland. However, the role of PREB in the adrenal gland is not clearly understood. Scavenger receptor class B type I (SR-BI) is a receptor for high-density lipoprotein that mediates the cellular uptake of high-density lipoprotein-cholesteryl ester and is a major route for cholesterol delivery to the steroidogenic pathway in the adrenal gland. In the present study, we have examined the role of PREB in regulating SR-BI. SR-BI expression was found to be regulated by cAMP, which stimulated the expression of PREB in a dose-dependent manner. Conversely, overexpression of PREB using a PREB-expressing adenovirus increased the expression of the SR-BI protein in the adrenocortical cell line Y-1. In addition, PREB induced the expression of the luciferase reporter protein that was under the control of the SR-BI promoter. EMSA showed that PREB mediates its transcriptional effect by binding to the PREB-responsive cis-element of the SR-BI promoter. Finally, we used small interfering RNA to inhibit PREB expression in the Y-1 cells and demonstrated that the knockdown of PREB expression attenuated the effects of cAMP on SR-BI expression. In summary, our data showed that in the adrenal gland, PREB regulates the transcription of the SR-BI gene via cAMP. (Endocrinology 149: 6103-6112, 2008)