Both, the mineralocorticoid receptor (MR) and its closest relative the glucocorticoid receptor (GR) act as ligand-bound transcription factors at a joint hormone response element. Whereas the MR affects electrolyte and water homeostasis and shows profibrotic and proinflammatory effects the GR acts antifibrotic and antiinflammatory Because of their different pathophysiological effects the existence of additional DNA-bindig elements has been postulated. Previously, we showed that ligand-bound MR mediates some pathophysiological effects by specific up-regulation of the epidermal growth factor receptor (EGFR) via enhanced EGFR promoter activity. Reporter-gene-assays with deletion constructs of the EGFR promoter identified a 65bp mineralocorticoid receptor response element (MRE) which does not interact with the GR. In vitro transcription factor binding assays with this MRE showed that activated MR does not bind directly to MRE by itself. We identified a binding motif for specificity protein 1 (SP1) within the MRE sequence using bioinformatical tools. The specific and direct binding of SP1 to MRE was confirmed by EMSA using biotinylated MRE probe and recombinant SP1. We also could show that MR binds specifically to MRE in our in vitro transcription factor binding assays only in the presence of SP1. Additionally, inhibition of SP1 with siRNA or a specific inhibitor abolished MR-mediated induction of EGFR expression which could be confirmed in different cell types (HEKs,HAoSMCs, A7r5). To identify hMR domains participating in the interaction with the MRE, we tested deletion constructs of the hMR in our MRE reporter gene assay. None of the deletion constructs by themselves could MR-dependently activate the MRE either in HEK or OK cells. With our experiments we identified a MR-specific response element which should be used as a fundament for a genome-wide screening for further MRE regulated genes.