Department of Biochemistry, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan.
Mol Cell Endocrinol. 2013 May 6;370(1-2):1-10. doi: 10.1016/j.mce.2013.02.012. Epub 2013 Feb 19.
Ferredoxin 1 (FDX1; adrenodoxin) is an iron-sulfur protein that is involved in various metabolic processes, including steroid hormone synthesis in mammalian tissues. We investigated the transcriptional regulation of FDX1 in ovarian granulosa cells. Previously, we reported that the NR5A family, including steroidogenic factor-1 (SF-1) and liver receptor homolog-1 could induce differentiation of human mesenchymal stem cells (hMSCs) into steroidogenic cells. A ChIP assay showed that SF-1 could bind to the FDX1 promoter in differentiated hMSCs. Luciferase reporter assays showed that transcription of FDX1 was synergistically activated by the NR5A family and 8Br-cAMP treatment through two SF-1 binding sites and a CRE-like sequence in a human ovarian granulosa cell line, KGN. Knockdown of FDX1 attenuated progesterone production in KGN cells. These results indicate transcription of FDX1 is regulated by the NR5A family and cAMP signaling, and participates in steroid hormone production in ovarian granulosa cells.
铁氧还蛋白 1（FDX1；肾上腺皮质酮）是一种参与多种代谢过程的铁硫蛋白，包括哺乳动物组织中的类固醇激素合成。我们研究了卵巢颗粒细胞中 FDX1 的转录调控。此前，我们报道 NR5A 家族（包括类固醇生成因子-1（SF-1）和肝受体同源物-1）可诱导人间充质干细胞（hMSC）分化为类固醇生成细胞。ChIP 分析表明，SF-1 可与分化的 hMSC 中的 FDX1 启动子结合。荧光素酶报告基因分析表明，NR5A 家族和 8Br-cAMP 处理通过人卵巢颗粒细胞系 KGN 中的两个 SF-1 结合位点和一个 CRE 样序列协同激活 FDX1 的转录。FDX1 的敲低减弱了 KGN 细胞中孕激素的产生。这些结果表明 FDX1 的转录受 NR5A 家族和 cAMP 信号的调节，并参与卵巢颗粒细胞中类固醇激素的产生。
