Mineralocorticoid receptors: emerging complexity and functional diversity

Area of Science:

• Endocrinology
• Molecular Biology
• Physiology

Background:

• Mineralocorticoid receptor (MR) activation by aldosterone is crucial for salt/fluid homeostasis and blood pressure.
• 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) was thought to ensure MR specificity by inactivating abundant glucocorticoids.

Purpose of the Study:

• To review emerging evidence challenging the traditional view of MR activation and specificity.
• To explore the complex mechanisms of MR action in diverse tissues.

Main Methods:

• Literature review of recent studies on MR activation, glucocorticoids, and 11beta-HSDs.
• Analysis of findings in both epithelial and non-epithelial tissues.

Main Results:

• Increasing evidence suggests 11beta-hydroxyglucocorticoids can act as MR antagonists in non-epithelial tissues (brain, heart, macrophages).
• Redox changes and signaling events appear critical for MR activation in these tissues.
• MR specificity is more complex than previously understood, varying by tissue type.

Conclusions:

• The traditional model of MR activation solely by aldosterone, facilitated by 11beta-HSD2, is insufficient.
• MR exhibits diverse physiological roles and functions influenced by tissue-specific mechanisms and signaling pathways.
• A nuanced understanding of MR regulation is essential for comprehending its multifaceted roles in health and disease.