Mineralocorticoid receptor signaling: crosstalk with membrane receptors and other modulators

The mineralocorticoid receptor (MR) belongs to the steroid receptor superfamily. Classically, it acts as a ligand-bound transcription factor in epithelial tissues, where it regulates water and electrolyte homeostasis and controls blood pressure. Additionally, the MR has been shown to elicit pathophysiological effects including inflammation, fibrosis and remodeling processes in the cardiovascular system and the kidneys and MR antagonists have proven beneficial for patients with certain cardiovascular and renal disease. The underlying molecular mechanisms that mediate MR effects have not been fully elucidated but very likely rely on interactions with other signaling pathways in addition to genomic actions at hormone response elements. In this review we will focus on interactions of MR signaling with different membrane receptors, namely receptor tyrosine kinases and the angiotensin II receptor because of their potential relevance for disease. In addition, GPR30 is discussed as a new aldosterone receptor. To gain insights into the problem why the MR only seems to mediate pathophysiological effects in the presence of additional permissive factors we will also briefly discuss factors that lead to modulation of MR activity as well. Overall, MR signaling is part of an intricate network that still needs to be investigated further.