Huang Y, Hu M, Hsu N, Wang C L, Chung B
Institute of Molecular Biology, 48, Academia Sinica, Nankang, Taipei, Taiwan.
Mol Cell Endocrinol. 2001 Apr 25;175(1-2):205-10. doi: 10.1016/s0303-7207(01)00388-4.
The CYP11A1 gene encodes cytochrome P450scc, the enzyme catalyzing the first step of steroid biosynthesis in the adrenal and gonad. We generated transgenic mice containing 2.3 kb of the 5'-flanking region of CYP11A1 driving LacZ reporter gene expression, in order to study hormonal control of CYP11A1 gene expression in different tissues. This 2.3 kb fragment contains information for hormonal control; by ACTH and hCG which increased reporter gene expression, in the adrenal and testis of transgenic mice respectively, while dexamethasone administration decreased reporter activity in the adrenal. The 5'-fragment of CYP11A1 has appreciable promoter activities in mouse adrenal Y1 cells but not in non-steroidogenic COS-1 cells, showing cell-type specificity. Transcription factor SF-1 activates the 2.3 kb promoter, which can be potentiated by cotransfection with c-Jun in steroidogenic JEG3 cells but not in COS-1 cells. We conclude that the 2.3 kb region of CYP11A1 contains elements controlling hormonal-dependent, cell-type-specific expression. In addition, c-Jun and SF-1 could act synergistically to activate CYP11A1 gene expression.
CYP11A1基因编码细胞色素P450scc，该酶催化肾上腺和性腺中类固醇生物合成的第一步。为了研究CYP11A1基因在不同组织中表达的激素调控，我们构建了含有CYP11A1基因5'侧翼区2.3 kb片段驱动LacZ报告基因表达的转基因小鼠。该2.3 kb片段包含激素调控信息；促肾上腺皮质激素（ACTH）和人绒毛膜促性腺激素（hCG）分别增加了转基因小鼠肾上腺和睾丸中报告基因的表达，而给予地塞米松则降低了肾上腺中的报告基因活性。CYP11A1基因的5'片段在小鼠肾上腺Y1细胞中具有明显的启动子活性，但在非类固醇生成的COS-1细胞中则没有，显示出细胞类型特异性。转录因子SF-1激活2.3 kb启动子，在类固醇生成的JEG3细胞中与c-Jun共转染可增强其活性，但在COS-1细胞中则不能。我们得出结论，CYP11A1基因的2.3 kb区域包含控制激素依赖性、细胞类型特异性表达的元件。此外，c-Jun和SF-1可能协同作用以激活CYP11A1基因的表达。
