Aldosterone: the minority hormone of the adrenal cortex

In comparison with the glucocorticoids cortisol and corticosterone, the mineralocorticoid aldosterone is a minority hormone of the mammalian adrenal cortex, and its proper function is dependent upon protective physiological mechanisms. These include a particular site of aldosterone synthesis in zona glomerulosa cells as well as a complex multifactorial control system, which adapts aldosterone production to acute and chronic changes in body sodium and potassium contents, irrespective of pituitary ACTH secretion. In the course of the last few years, an important element of these mechanisms has been identified in the form of the enzyme involved in the final steps of aldosterone biosynthesis. In species such as the human, rat, and mouse, the conversion of deoxycorticosterone to aldosterone is catalyzed by an isozyme (CYP11B2) of cytochrome P450(11 beta) (CYB11B1). The gene encoding this enzyme is expressed only in the zona glomerulosa. Its transcription is enhanced by sodium deficiency and potassium intake, but is suppressed by long-term administration of high doses of ACTH. In contrast, the gene encoding CYP11B1, i.e., the major (non-aldosterone-producing) type of the enzyme, is expressed mainly in the zona fasciculata, and its expression depends on physiological concentrations of ACTH. In other animal species (cattle, pig), the major forms of cytochrome P450(11) beta have an inherent aldosterone-synthesizing activity, which is, however, selectively suppressed in mitochondria of zona fasciculata cells by yet unknown mechanisms.