Structural and molecular determinants of mineralocorticoid receptor signalling

Br J Pharmacol. 2022 Jul;179(13):3103-3118. doi: 10.1111/bph.15746. Epub 2021 Dec 12.

Abstract

During the past decades, the mineralocorticoid receptor (MR) has evolved from a much-overlooked member of the steroid hormone receptor family to an important player, not only in volume and electrolyte homeostasis but also in pathological changes occurring in an increasing number of tissues, especially the renal and cardiovascular systems. Simultaneously, a wealth of information about the structure, interaction partners and chromatin requirements for genomic signalling of steroid hormone receptors became available. However, much of the information for the MR has been deduced from studies of other family members and there is still a lack of knowledge about MR-specific features in ligand binding, chromatin remodelling, co-factor interactions and general MR specificity-conferring mechanisms that can completely explain the differences in pathophysiological function between MR and its closest relative, the glucocorticoid receptor. This review aims to give an overview of the current knowledge of MR structure, signalling and co-factors modulating its activity. 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.

Keywords: aldosterone; corticosteroid receptors; glucocorticoids; nuclear receptors.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aldosterone
  • Receptors, Glucocorticoid
  • Receptors, Mineralocorticoid* / metabolism
  • Signal Transduction*

Substances

  • Receptors, Glucocorticoid
  • Receptors, Mineralocorticoid
  • Aldosterone