Watanabe M, Nakajin S
Department of Biochemistry, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa, Tokyo 142-8501, Japan.
J Endocrinol. 2004 Jan;180(1):125-33. doi: 10.1677/joe.0.1800125.
A number of conditions related to sex-reversal in boys and men and precocious puberty in girls are caused by estrogen-secreting adrenal tumors. In these tumors, cytochrome P450 aromatase (aromatase) that is encoded in the CYP19 gene is expressed at high levels. To investigate the molecular mechanism of aromatase expression in these adrenal tumors, we characterized the activity, gene transcript and genomic promoter region of aromatase in the human adrenocortical carcinoma cell line H295R. Aromatase activity and the transcript of the CYP19 gene were highly up-regulated by forskolin, but not by dexamethasone. The results from exon I-specific reverse transcriptase (RT)-PCR and the transfection of reporter constructs suggested that promoter I.3 and promoter II were activated in H295R. Deletion and mutation analysis suggested that cAMP response element-like sequence (CLS) and steroidogenic factor-1 (SF-1) motif, were critical for the activation of promoter II. The results of this work should provide the basis for the molecular analysis of aromatase expression in adrenocortical cells.
一些与男孩和男性性别反转以及女孩性早熟相关的病症是由分泌雌激素的肾上腺肿瘤引起的。在这些肿瘤中，由CYP19基因编码的细胞色素P450芳香化酶（芳香化酶）高水平表达。为了研究这些肾上腺肿瘤中芳香化酶表达的分子机制，我们对人肾上腺皮质癌细胞系H295R中芳香化酶的活性、基因转录本和基因组启动子区域进行了表征。芳香化酶活性和CYP19基因的转录本被福司可林高度上调，但地塞米松未使其上调。外显子I特异性逆转录酶（RT）-PCR和报告基因构建体转染的结果表明，启动子I.3和启动子II在H295R中被激活。缺失和突变分析表明，环磷酸腺苷反应元件样序列（CLS）和类固醇生成因子-1（SF-1）基序对启动子II的激活至关重要。这项工作的结果应为肾上腺皮质细胞中芳香化酶表达的分子分析提供依据。
