Mineralocorticoid Physiology and Electrolyte Regulation

Mineralocorticoids, principally aldosterone, are steroid hormones from the zona glomerulosa that regulate sodium and potassium balance and, through them, extracellular fluid volume and blood pressure. Aldosterone acts mainly on the distal nephron to promote sodium reabsorption and potassium secretion, and its release is governed chiefly by the renin-angiotensin system and plasma potassium.

Definition

Mineralocorticoid physiology is the study of how aldosterone, secreted by the adrenal zona glomerulosa, acts via the mineralocorticoid receptor in the distal nephron to control sodium reabsorption and potassium excretion, thereby regulating extracellular fluid volume, electrolyte balance, and blood pressure.

Scope

This topic covers aldosterone's regulation and renal actions, the mineralocorticoid receptor and the mechanism by which it remains aldosterone-selective despite cortisol's higher concentration, and the role of mineralocorticoids in fluid-electrolyte and blood-pressure homeostasis. Synthesis is covered in the adrenocortical synthesis topic.

Core questions

• What stimuli regulate aldosterone secretion, and why are the renin-angiotensin system and potassium the dominant ones?
• How does aldosterone change renal handling of sodium and potassium at the cellular level?
• How does the mineralocorticoid receptor remain selective for aldosterone when cortisol circulates at much higher concentrations?

Key concepts

• Aldosterone
• Mineralocorticoid receptor (MR)
• Renin-angiotensin-aldosterone system (RAAS)
• Angiotensin II as the main stimulus
• Plasma potassium as a direct stimulus
• Distal nephron sodium reabsorption (ENaC, Na/K-ATPase)
• Potassium and hydrogen ion secretion
• 11-beta-HSD2 and aldosterone selectivity

Mechanisms

Aldosterone secretion from the zona glomerulosa is driven principally by angiotensin II, generated by the renin-angiotensin system in response to reduced renal perfusion or low sodium delivery, and by elevated plasma potassium acting directly on glomerulosa cells; ACTH has only a minor, transient effect. Once secreted, aldosterone enters principal cells of the distal tubule and collecting duct, binds the cytoplasmic mineralocorticoid receptor, and induces transcription of proteins that increase apical epithelial sodium channel (ENaC) activity and basolateral Na/K-ATPase, raising sodium reabsorption while promoting potassium and hydrogen ion secretion. Because cortisol binds the mineralocorticoid receptor with similar affinity, selectivity is maintained in these tissues by the enzyme 11-beta-hydroxysteroid dehydrogenase type 2, which converts cortisol to inactive cortisone locally, leaving the receptor available to aldosterone.

Clinical relevance

Mineralocorticoid physiology explains the consequences of aldosterone excess (such as hypertension with hypokalemia in primary aldosteronism) and deficiency (such as salt wasting and hyperkalemia in aldosterone deficiency), and why impaired 11-beta-HSD2 activity can produce a syndrome of apparent mineralocorticoid excess. This entry is a physiological reference and does not provide diagnostic or treatment guidance for any individual.

Evidence & guidelines

The regulation and renal actions of aldosterone and the basis of receptor selectivity are established physiology described in standard texts, with angiotensin II signaling reviewed comprehensively by Forrester et al. (2018). The clinical condition of aldosterone excess is addressed by an Endocrine Society guideline (Funder et al., 2016), which lies beyond this entry's physiological scope and is cited for orientation only.

History

Aldosterone was isolated and characterized in the early 1950s by Simpson, Tait, and colleagues, who identified the previously unknown 'electrocortin' as the principal salt-retaining adrenal steroid. Soon after, Jerome Conn described primary aldosteronism, demonstrating the clinical importance of mineralocorticoid excess. The later discovery that 11-beta-HSD2 protects the receptor from cortisol resolved the long-standing puzzle of how aldosterone selectivity is achieved.

Key figures

• James Tait
• Sylvia Tait
• John Funder
• Jerome Conn

Seminal works

• forrester-2018
• funder-2016

Frequently asked questions

What is the main stimulus for aldosterone secretion?

Angiotensin II, produced by the renin-angiotensin system, is the principal stimulus, together with a direct effect of elevated plasma potassium on glomerulosa cells. ACTH has only a minor and transient role.

If cortisol can bind the mineralocorticoid receptor, why doesn't it act like aldosterone in the kidney?

Aldosterone-target cells express 11-beta-hydroxysteroid dehydrogenase type 2, which converts cortisol to inactive cortisone locally, so the mineralocorticoid receptor remains available to respond to aldosterone.