Transcriptional regulation of human ferredoxin 1 in ovarian granulosa cells

► cAMP stimulation rapidly increases the expression of FDX1 in the rat ovarian granulosa cells. ► In differentiated hMSCs, SF-1 binds to the promoter of FDX1. ► Two SF-1 binding sites and a CRE-like sequence affect the FDX1 promoter activity. ► NR5A family and cAMP synergistically activate transcription from the FDX1 promoter. 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.