Gurates Bilgin, Amsterdam Abraham, Tamura Mitsutoshi, Yang Sijun, Zhou Jianfeng, Fang Zongjuan, Amin Sanober, Sebastian Siby, Bulun Serdar E
Departments of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, University of Illinois at Chicago, 820 S Wood Street, M/C 808, Chicago, IL 60612, USA.
Mol Cell Endocrinol. 2003 Oct 31;208(1-2):61-75. doi: 10.1016/s0303-7207(03)00198-9.
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.
类固醇生成因子-1（SF-1）对大多数类固醇生成基因启动子的结合活性，作为对促性腺激素的应答，是调节性腺中类固醇生成的关键机制。因此，SF-1作用的调节对于卵巢中性类固醇生成的差异调节可能至关重要。芳香化酶P450（P450arom）是雌激素形成的限速酶。在本研究中，我们鉴定了性腺芳香化酶启动子中的另一个核受体半位点，我们证明其对芳香化酶调节很重要。我们在此还表明，在卵巢颗粒细胞、睾丸支持细胞和JEG-3绒毛膜癌细胞中，SF-1对P450arom启动子活性的刺激受到两种转录因子的抑制，即威尔姆斯肿瘤抑制基因（WT1）和X染色体基因1上的剂量敏感性性别反转先天性肾上腺发育不全关键区域（DAX-1）。鉴于这些转录因子在性腺发育和功能中的特定作用，WT1和DAX-1对SF-1作用的调节可能代表了类固醇生成中的一个重要关键机制。
