Steroidogenic Factor-1 Influences Protein-Deoxyribonucleic Acid Interactions within the Cyclic Adenosine 3',5'-Monophosphate-Responsive Regions of the Murine Steroidogenic Acute Regulatory Protein Gene

De novo synthesis of the steroidogenic acute regulatory protein (StAR) in response to trophic hormonal stimulation of steroidogenic cells is required for the delivery of cholesterol from the mitochondrial outer membrane to the mitochondrial inner membrane and the cy- tochrome P450 side-chain cleavage enzyme. StAR expression is tran- scriptionally regulated by cAMP-mediated mechanisms, and we have identified a 45-bp region within the mouse promoter that is important for cAMP responsiveness of the gene. This region, located between 2105 and 260 of the start site of transcription, contains a SF-1- binding site, a highly conserved C/EBPb 2AP-1-nuclear receptor half- site sequences (CAN region), and a GATA-4-binding site. The SF-1 element and CAN region are required for full basal activity, whereas the GATA-4 element may account for 20% of the cAMP response in MA-10 mouse Leydig tumor cells. A cAMP-dependent protein-DNA complex was observed with the CAN region and mutation of a non- consensus AP-1 site within this region greatly diminished promoter strength. Complex protein-DNA interactions within the cAMP re- sponse region (2105/260) were shown to require the SF-1 element (295), suggesting that SF-1 is required for protein-DNA interaction at the CAN (279) region and maximal activity of the promoter. (En- docrinology 141: 1345-1355, 2000)