**2. Synthesis of Aldosterone**

The primary function of aldosterone is to maintain fluid and electrolyte balance for the control of blood pressure. The main physiological regulators of aldosterone synthesis are angiotensin II, potassium and adrenocorticotropic hormone. Aldosterone synthesis is restricted to the *zona glomerulosa* (ZG), the outer layer of the adrenal cortex (Figure 1) where aldosterone synthase converts deoxycorticosterone to aldosterone by three successive steps of 11β-hydroxylation, 18-hydroxylation and 18-oxidation by a single enzyme, aldosterone synthase (encoded by *CYP11B2*). *CYP11B2* displays a high level of intron and exon sequence homology to the *CYP11B1* gene localized in the *zona fasciculata* (ZF) that encodes 11β-hydroxylase that catalyses the final step in the conversion of 11-deoxycortisol to cortisol (Figure 1). Angiotensin II and potassium regulate aldosterone production via Ca2+ signalling which also plays a key role in the aldosterone excess in PA due to the somatic and germline mutations in ion channels and transporters.

**Figure 1.** Aldosterone synthesis in the adrenal cortex. Aldosterone is synthesized in the *zona glomerulosa* (ZG) distinct from the synthesis of cortisol in the *zona fasciculata* (ZF). Aldosterone synthase encoded by *CYP11B2* performs all three enzymatic steps in the conversion of deoxycorticosterone to aldosterone.
