What is the source and function of aldosterone in the human body?

Aldosterone: Source and Function

Aldosterone is secreted from the zona glomerulosa of the adrenal cortex and functions primarily to regulate sodium homeostasis and blood pressure by promoting sodium reabsorption and potassium excretion in the renal collecting duct. 1, 2

Site of Secretion

• Aldosterone is synthesized and secreted exclusively from the zona glomerulosa, the outermost layer of the adrenal cortex. 1, 2
• The zona glomerulosa cells are intrinsic electrical oscillators that generate spontaneous membrane potential oscillations, providing the calcium signaling platform necessary for aldosterone production. 3
• These specialized adrenal cells produce aldosterone through a series of enzymatic conversions from cholesterol, with regulation occurring at two critical steps: cholesterol to pregnenolone (early pathway) and corticosterone to aldosterone via aldosterone synthase (late pathway). 4

Primary Functions

Renal and Cardiovascular Effects

• Aldosterone's primary function is regulating sodium and water homeostasis by binding to mineralocorticoid receptors in the renal cortical collecting duct, where it promotes sodium reabsorption in exchange for potassium and hydrogen ion secretion. 1, 5
• This sodium retention expands extracellular fluid volume, which directly increases blood pressure and suppresses renin secretion through negative feedback. 1
• Aldosterone acts as both a diuretic antagonist and antihypertensive regulator by controlling the aldosterone-dependent sodium-potassium exchange site in the distal convoluted renal tubule. 5

Non-Hypertensive Effects

• Beyond blood pressure regulation, aldosterone exerts direct toxic effects on multiple organ systems, including the heart, kidneys, and vasculature, independent of its hypertensive effects. 6, 7, 8
• Aldosterone contributes to cardiac fibrosis, myocardial hypertrophy, heart failure, arrhythmias, vascular remodeling, endothelial dysfunction, perivascular inflammation, and progressive renal tubular damage. 6, 8
• These tissue effects occur through both genomic mechanisms (direct DNA transcription modulation) and rapid non-genomic pathways in epithelial and non-epithelial tissues. 8

Regulation of Secretion

• Aldosterone production is primarily regulated by the renin-angiotensin-aldosterone system (RAAS), specifically by angiotensin II, and secondarily by serum potassium levels. 2, 8, 4
• Elevated serum potassium and angiotensin II stimulate aldosterone secretion, while ACTH, neural mediators, and natriuretic factors provide additional short-term regulatory control. 8, 4
• In primary aldosteronism, aldosterone production becomes autonomous and independent of the renin-angiotensin system, remaining non-suppressible even with dietary sodium loading. 1

Clinical Significance

• Insufficient aldosterone secretion leads to hypotension and circulatory shock, particularly in infancy, while excessive aldosterone causes hypertension and accelerates end-organ damage. 2
• Patients with primary aldosteronism have dramatically worse cardiovascular outcomes than those with primary hypertension at equivalent blood pressure levels, including 3.7-fold increased heart failure, 4.2-fold increased stroke, and 12.1-fold increased atrial fibrillation risk. 9
• The deleterious effects of aldosterone overproduction are often reversible with unilateral laparoscopic adrenalectomy or mineralocorticoid receptor antagonist treatment, which can improve cardiac and kidney function parameters. 6