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In human metabolism the biosynthesis of aldosterone largely depends on the metabolism of cholesterol. Cholesterol is metabolized in what is known as the early pathway of aldosterone synthesis [12] and is hydroxylated becoming (20R,22R)-dihydroxycholesterol which is then metabolized as a direct precursor to pregnenolone.
Moreover, aldosterone synthase is found within the zona glomerulosa at the outer edge of the adrenal cortex; 11β-hydroxylase is found in the zona glomerulosa and zona fasciculata. Steroidogenesis, showing aldosterone synthesis at upper-right corner. [13] Aldosterone synthase is normally absent in other sections of the adrenal gland. [14]
The outermost layer, the zona glomerulosa is the main site for the production of aldosterone, a mineralocorticoid. The synthesis and secretion of aldosterone are mainly regulated by the renin–angiotensin–aldosterone system. The zona glomerulosa cells express a specific enzyme aldosterone synthase (also known as CYP11B2).
In the adrenal cortex, angiotensin II acts to cause the release of aldosterone. Aldosterone acts on the tubules (e.g., the distal convoluted tubules and the cortical collecting ducts) in the kidneys, causing them to reabsorb more sodium and water from the urine. This increases blood volume and, therefore, increases blood pressure.
18-Hydroxylase (aldosterone synthase) – mineralocorticoid synthesis 21-Hydroxylase – corticosteroid synthesis Cytochrome P450 ( CYP1 , 2 , 3 ) – estrogen metabolism
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). [citation needed] Aldosterone synthesis is stimulated by several factors: [citation needed]
The synthesis of adrenocortical steroid hormones involves a chain of oxidation-reduction reactions catalyzed by a series of enzymes. Synthesis begins with a molecule of cholesterol. Through shared intermediates and pathways branching off those shared intermediates, the different classes of steroids are synthesized.
The major pathway for aldosterone production is in the adrenal glomerulosa zone of the adrenal gland. It is not a major secretory hormone. It is produced from progesterone by 21β-hydroxylase and is converted to corticosterone by 11β-hydroxylase. Corticosterone is then converted to aldosterone by aldosterone synthase. [10]