The mineralocorticoid receptor (MR or NR3C2) is expressed in all types of cells from the different skin compartments. The binding and activation by glucocorticoids has a higher affinity than that on the closely related glucocorticoid receptor (GR or NR3C1). As both corticosteroid receptors are co-express in the skin and considering the therapeutic relevance of glucocorticoids to combat skin inflammatory diseases, it was proposed that several of the major side effects of topical glucocorticoids, such as skin atrophy and delayed wound healing, were due to unintended activation of the MR. Indeed, cutaneous MR blockade using genetic and pharmacological approaches in mice and human reduced corticosteroid-associated skin atrophy in conditions of endogenous and pharmacological glucocorticoid excess. Although data support the safety of topical MR antagonists combined with glucocorticoid, it is crucial to address the efficacy of treatment in skin inflammatory conditions and its impact on the overall metabolism. LINKED ARTICLES: This article is part of a themed issue on Emerging Fields for Therapeutic Targeting of the Aldosterone-Mineralocorticoid Receptor Signaling Pathway. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.13/issuetoc.
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