Targeting activated mineralocorticoid receptor: Occam's razor revisited

Area of Science:

• Endocrinology
• Molecular Biology
• Pathology

Background:

• Mineralocorticoid receptors (MRs) are traditionally linked to electrolyte transport.
• Emerging evidence shows MR activation contributes to tissue inflammation and fibrosis.
• Aldosterone is a primary MR activator, but endogenous glucocorticoids can also activate MR under specific conditions.

Purpose of the Study:

• To elucidate the mechanisms of MR activation beyond aldosterone.
• To investigate the role of endogenous glucocorticoids in MR activation.
• To explore factors influencing glucocorticoid-induced MR activation.

Main Methods:

• Review of existing literature on MR signaling pathways.
• Analysis of studies investigating glucocorticoid interactions with MR.
• Examination of the role of 11β-hydroxysteroid dehydrogenase and reactive oxygen species in MR regulation.

Main Results:

• Endogenous glucocorticoids (cortisol, corticosterone) can activate MR.
• Tissue-specific enzymes like 11β-hydroxysteroid dehydrogenase typically limit glucocorticoid-induced MR activation.
• Reactive oxygen species can promote glucocorticoid-induced MR activation, independent of aldosterone.

Conclusions:

• MR activation has broader implications than electrolyte balance, including inflammatory and fibrotic processes.
• Glucocorticoid-induced MR activation is a significant pathway, modulated by local enzymatic activity and oxidative stress.
• Understanding these pathways is crucial for developing targeted therapies for MR-related diseases.