Aldosterone Research: 65 Years, and Counting

Area of Science:

• Endocrinology
• Nephrology
• Molecular Biology

Background:

• Aldosterone, a mineralocorticoid hormone, regulates electrolyte homeostasis primarily in epithelial tissues via the mineralocorticoid receptor (MR).
• Mineralocorticoid receptors (MRs) are widely distributed beyond known aldosterone target tissues.
• MRs exhibit high affinity for glucocorticoids and progesterone, not just aldosterone.

Observation:

• In specific tissues like epithelia and the brain's nucleus tractus solitarius, MRs are protected from high-circulating cortisol by 11β-hydroxysteroid dehydrogenase, which inactivates cortisol.
• Tissues lacking this protective enzyme are primarily influenced by cortisol, which circulates at much higher concentrations than aldosterone.
• Cortisol-occupied MRs have emerging roles, particularly as agonists in damaged tissues, mirroring experimental aldosterone effects.

Findings:

• Aldosterone's established physiological roles are confined to epithelial actions, the blood vessel wall, and the nucleus tractus solitarius.
• Cortisol can activate MRs in tissues lacking 11β-hydroxysteroid dehydrogenase, with significant implications in pathophysiological conditions.
• Evidence suggests aldosterone's pathophysiological roles are limited to its known epithelial and specific neural/vascular actions.

Implications:

• Re-evaluation of aldosterone's exclusive role in mineralocorticoid actions is necessary.
• Understanding cortisol's interaction with MRs is crucial for comprehending tissue-specific steroid hormone effects.
• This research highlights the complex interplay of hormones and receptors in maintaining homeostasis and disease pathogenesis.