aldosterone

Synthesis

The corticosteroids are synthesized from cholesterol within the adrenal cortex. Most steroidogenic reactions are catalysed by enzymes of the cytochrome P450 family. They are located within the mitochondria and require adrenodoxin as a cofactor (except 21-hydroxylase and 17α-hydroxylase).

Aldosterone and corticosterone share the first part of their biosynthetic pathway. The last part is either mediated by the aldosterone synthase (for aldosterone) or by the 11β-hydroxylase (for corticosterone). These enzymes are nearly identical (they share 11β-hydroxylation and 18-hydroxylation functions). But aldosterone synthase is also able to perform a 18-oxidation. Moreover, aldosterone synthase is found within the zona glomerulosa at the outer edge of the adrenal cortex; 11β-hydroxylase is found in the zona fasciculata and reticularis.

Note: aldosterone synthase is absent in other sections of the adrenal gland.

Function

It is the sole endogenous member of the class of mineralocorticoids in human (corticosterone in rodent). It functions in two main locations of the kidney:

• at distal tubule: Acting on mineralocorticoid receptors (MR) on principal cells in the distal tubule of the kidney nephron, it increases the permeability of their apical (luminal) membrane to potassium and sodium and activates their basolateral Na⁺/K⁺ pumps, stimulating ATP hydrolysis, reabsorbing sodium (Na⁺) ions and water into the blood, and secreting potassium (K⁺) ions into the urine.

• at collecting duct: Aldosterone also stimulates H⁺ secretion by principal cells in the collecting duct, regulating plasma bicarbonate (HCO3⁻) levels and its acid/base balance.^[1]

Aldosterone is responsible for the reabsorption of about 2% of filtered sodium in the kidneys, which is nearly equal to the entire sodium content in human blood under normal GFR (glomerular filtration rate).^[2]

Location of receptors

Unlike neuroreceptors, classic steroid receptors are intracellularly located. The aldosterone/MR receptor complex binds on the DNA to specific hormone response element, which leads to gene specific transcription.

Some of the transcribed genes are crucial for transepithelial sodium transport, including the three subunits of the epithelial sodium channel, the Na⁺/K⁺ pumps and their regulatory proteins serum and glucocorticoid-induced kinase, and channel-inducing factor respectively.

Stimulation of synthesis

Aldosterone synthesis is stimulated by several factors:

• by increased plasma angiotensin II, ACTH, or potassium levels, which are present in proportion to plasma sodium deficiencies. (The increased potassium level works to regulate aldosterone synthesis by depolarizing the cells in the zona glomerulosa, which opens the voltage-dependent calcium channels.)

• by plasma acidosis.

• by the stretch receptors located in the atria of the heart. If decreased blood pressure is detected, the adrenal gland is stimulated by these stretch receptors to release aldosterone, which increases sodium reabsorption from the urine, sweat and the gut. This causes increased osmolarity in the extracellular fluid which will eventually return blood pressure toward normal.

The secretion of aldosterone has a diurnal rhythm.^[3]

Control of aldosterone release in the kidney

• The role of the renin-angiotensin system
• The role of sympathetic nerves
• The role of baroreceptors
• The role of the juxtaglomerular apparatus
• The plasma concentration of potassium

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