WT1 and DAX-1 regulate SF-1-mediated human P450arom gene expression in gonadal cells
WT1 and DAX-1 regulate SF-1-mediated human P450arom gene expression in gonadal cells
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DOI：
10.1016/s0303-7207(03)00198-9
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发表时间：
2003-10-31
影响因子：
4.1
通讯作者：
Bulun, SE
中科院分区：
文献类型：
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作者：
Gurates, B;Amsterdam, A;Bulun, SE
类固醇生成因子-1（SF-1）与大多数类固醇生成基因启动子的结合活性是调节性腺中类固醇生成的关键机制。因此，SF-1作用的调节可能是卵巢中性类固醇形成的差异调节所必需的。芳香化酶P450（P450 arom）是雌激素形成的限速酶。在这项研究中，我们的特点是另一个核受体半位点的性腺芳香化酶启动子，我们证明是重要的芳香化酶的调节。我们还发现，SF-1对卵巢颗粒细胞、睾丸Sertoli细胞和JEG-3绒毛膜癌细胞中P450 arom启动子活性的刺激作用受到两种转录因子的抑制，即Wilms肿瘤抑制基因（WT 1）和X染色体基因1上剂量敏感性逆转先天性肾上腺发育不全关键区（DAX-1）。鉴于这些转录因子在性腺发育和功能中的特征性作用，WT 1和DAX-1对SF-1作用的调节可能代表类固醇生成中的重要关键机制。(C)2003爱思唯尔爱尔兰有限公司保留所有权利。
Binding activity of steroidogenic factor-1 (SF-1) to promoters of the majority of steroidogenic genes in response to gonadotropins is a critical mechanism that regulates steroidogenesis in gonads. Thus, the modulation of SF-1 action may be essential for the differential regulation of formation of sex steroids in the ovary. Aromatase P450 (P450arom) is the rate-limiting enzyme for estrogen formation. In this study, we characterize another nuclear receptor half site in the gonadal aromatase promoter which we show to be important for aromatase regulation. We also show herein that the stimulation of P450arom promoter activity by SF-1 in ovarian granulosa, testicular Sertoli and JEG-3 choriocarcinoma cells is inhibited by two transcription factors, Wilms' tumor suppressor gene (WT1) and dosage sensitive sex reversal adrenal hypoplasia congenita critical region on the X chromosome gene 1 (DAX-1). Given the characterized roles of these transcription factors in gonadal development and function, modulation of SF-1 action by WT1 and DAX-1 may represent an important key mechanism in steroidogenesis. (C) 2003 Elsevier Ireland Ltd. All rights reserved.