Characterization of the promoter region of the mouse gene encoding the steroidogenic acute regulatory protein.
Characterization of the promoter region of the mouse gene encoding the steroidogenic acute regulatory protein.
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DOI：
10.1210/mend.11.2.9880
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发表时间：
1997-02
影响因子：
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通讯作者：
K. Caron;Y. Ikeda;Shiu Ching Soo;D. Stocco;K. Parker;B. Clark
中科院分区：
文献类型：
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作者：
K. Caron;Y. Ikeda;Shiu Ching Soo;D. Stocco;K. Parker;B. Clark
类固醇生成急性调节蛋白（星星）将胆固醇递送到线粒体内膜，在那里胆固醇侧链裂解酶进行类固醇激素生物合成的第一个关键步骤。星星表达仅限于类固醇生成细胞，并通过营养激素或cAMP处理迅速诱导。我们分析了小鼠星星基因的5 '侧翼区，以阐明调节其细胞特异性和细胞诱导表达的机制。在瞬时转染试验中，由星星5 '侧翼区驱动的荧光素酶报告基因以cAMP响应方式优先由类固醇生成Y1肾上腺皮质和MA-10 Leydig细胞表达。5 '-缺失和定点诱变研究鉴定了-254和-113之间的区域，该区域对于启动子活性的完整水平是必需的。该区域含有孤儿核受体类固醇生成因子-1（SF-1）的结合位点，虽然该结合位点不是激素诱导所必需的，但对基础启动子活性至关重要，因此暗示SF-1参与星星表达。对SF-1基因敲除小鼠的分析进一步支持SF-1在星星基因表达中的重要作用。这些研究为调节星星基因表达的机制提供了新的见解，并扩展了我们对SF-1在类固醇生成细胞中的全球作用的理解。
Steroidogenic acute regulatory protein (StAR) delivers cholesterol to the inner mitochondrial membrane, where the cholesterol side-chain cleavage enzyme carries out the first committed step in steroid hormone biosynthesis. StAR expression is restricted to steroidogenic cells and is rapidly induced by treatment with trophic hormones or cAMP. We analyzed the 5'-flanking region of the mouse StAR gene to elucidate the mechanisms that regulate its cell-specific and hormone-induced expression. In transient transfection assays, a luciferase reporter gene driven by the StAR 5'-flanking region was preferentially expressed by steroidogenic Y1 adrenocortical and MA-10 Leydig cells in a cAMP-responsive manner. 5'-Deletion and site-directed mutagenesis studies identified a region between -254 and -113 that is essential for full levels of promoter activity. This region contains a binding site for the orphan nuclear receptor steroidogenic factor-1 (SF-1) that, although not required for hormone induction, is critical for basal promoter activity, thus implicating SF-1 in StAR expression. Analyses of knockout mice deficient in SF-1 further supported an important role for SF-1 in StAR gene expression. These studies provide novel insights into the mechanisms that regulate StAR gene expression and extend our understanding of SF-1's global roles within steroidogenic cells.