The mineralocorticoid receptor (MR) belongs to the steroid receptor superfamily and acts as a ligand-dependent transcription factor with aldosterone as endogenous ligand. Physiologically, aldosterone and MR are involved in salt and water homeostasis and thereby long-term blood pressure regulation. However, activated MR can also induce pathophysiological effects in the renocardiovascular system leading to inflammation, endothelial dysfunction and remodeling processes. In clinical trials, MR inhibitors significantly improve mortality and morbidity in patiens with heart failure or after myocardial infarction. The underlying mechanism for these pathophysiological MR effects is not clear, especially since the MR shares a common hormone-response-element with its closest relative, the glucocorticoid receptor (GR) which elicits different effects and shows anti-inflammatory properties. One possible mechanistical explanation for pathophysiological MR effects is a cross-talk between MR and other signaling pathways. One promising interaction candidate with potential to mediate pathophysiological MR effects is the epidermal growth factor receptor (EGFR). The EGFR is a membrane receptor with tyrosine kinase activity that leads to proliferation, vasoconstriction and migration of cells. Additionally, many vasoactive substances like angiotensin II, endothelin-1 and phenylephrine also induce vascular remodeling and mediate at least part of their pathophysiological effects by transactivating the EGFR. We could show that a cross-talk between MR and EGFR signaling takes place both on the functional and transcriptional level. On the one hand, MR can enhance EGFR signaling by transactivating the EGFR, which then leads to enhanced phosphorylation of ERK. A key player involved in this interaction is the kinase c-src. Overall consequence of this cross-talk is facilitation of nuclear shuttling of MR and thereby induction of classical genomic MR signaling and modification of extracellular matrix composition. On the other hand, activated MR can induce EGFR expression by enhancing EGFR promoter activity. Characterization of the interaction partners identified a 65 bp mineralocorticoid response element (MRE) on the EGFR promoter. Furthermore, SP1 was discovered as a cofactor binding to MRE and necessary for binding of MR to EGFR promoter. MR mutants lacking the N-terminal A/B domain were not able to induce promoter activity, suggesting that the N-terminus of the MR interacts with SP1 at the mineralocorticoid response element to induce EGFR expression. Importantly, no change in EGFR promoter activity was detectable with activated GR, thus suggesting an MR specific effect. Overall, activated MR is able to transactivate and induce the expression of EGFR, which provides possible mechanisms underlying MR-specific pathophysiological effects in the renocardiovascular system.