Transcriptional repression of the rat steroidogenic acute regulatory (StAR) protein gene by the AP-1 family member c-Fos

Abstract

PGF2α, working via protein kinase C, may inhibit transcription of the StAR gene through negative regulatory factors. Administration of PGF2α increased c-Fos mRNA with a corresponding reduction in StAR mRNA. A search of the rat StAR promoter revealed three putative AP-1 elements at bp positions −85, −187 and −1561, which demonstrated specific binding of c-Fos by mobility shift assays. Co-transfection of c-Fos with the p-1862 StAR promoter caused a reduction in luciferase activity in the presence or absence of cAMP. Mutation of all three AP-1 sites in the p-1862 StAR promoter abolished c-Fos repression. Mutation of the proximal AP-1 site in the p-1862 StAR promoter reduced SF-1 mediated induction. This study is the first to demonstrate that c-Fos represses StAR gene transcription and adds to the current knowledge on the complex relationship that exists between SF-1 and c-Fos in the regulation of StAR activity.