Manna Pulak R, Wang Xing-Jia, Stocco Douglas M
Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
Steroids. 2003 Dec;68(14):1125-34. doi: 10.1016/j.steroids.2003.07.009.
The rate-limiting, committed, and regulatable step in steroid hormone biosynthesis is the transport of cholesterol from the outer to the inner mitochondrial membrane, a process that is mediated by the steroidogenic acute regulatory (StAR) protein. In steroidogenic cells, the StAR protein is regulated by cAMP-dependent mechanisms. However, the StAR promoter lacks a consensus cAMP response-element (CRE), suggesting the involvement of alternate regulatory factor(s) in cAMP responsiveness. These regulatory elements are found to be located in a transcription factor-binding site-rich region (consisting of approximately 150 nucleotides upstream of the transcription start site) of the StAR promoter, and appears to be the most important region in regulating transcription of the StAR gene. The StAR promoter sequences in mouse, rat and human are highly homologous, and in the absence of a canonical CRE, multiple cis-elements have been shown to be instrumental in the regulation of StAR gene expression. Nevertheless, it has become apparent that functional cooperation, interaction, and alteration of different transcription factors are involved in the fine-tuning of the regulatory events associated with StAR gene transcription.
类固醇激素生物合成中的限速、关键且可调节步骤是胆固醇从线粒体外膜转运至内膜，这一过程由类固醇生成急性调节（StAR）蛋白介导。在类固醇生成细胞中，StAR蛋白受cAMP依赖性机制调控。然而，StAR启动子缺乏一致的cAMP反应元件（CRE），这表明存在其他调节因子参与cAMP反应性。这些调节元件位于StAR启动子富含转录因子结合位点的区域（转录起始位点上游约150个核苷酸处），并且似乎是调节StAR基因转录的最重要区域。小鼠、大鼠和人类的StAR启动子序列高度同源，在缺乏典型CRE的情况下，多个顺式元件已被证明在调节StAR基因表达中起作用。尽管如此，不同转录因子的功能协作、相互作用和改变显然参与了与StAR基因转录相关的调节事件的微调。
