Final steps of aldosterone biosynthesis: molecular solution of a physiological problem

Abstract

The final two steps of aldosterone biosynthesis play a key role in the complex physiological adaptation of aldosterone secretion to changes in sodium and potassium content of the mammalian organism. The nature and identity of the enzyme catalyzing these steps have only recently been established. In the rat as well as in the human adrenal, two types of cytochrome P-450(11 beta) are encoded by two different genes. The major type of the enzyme catalyzes only the conversion of deoxycorticosterone to corticosterone or 18-hydroxy-11-deoxycorticosterone; it is present in all the zones of the adrenal cortex. The second type of the enzyme catalyzes the three steps involved in the conversion of deoxycorticosterone to aldosterone and occurs only in the zona glomerulosa. In rat zona glomerulosa cells, separate control systems independently regulate the expression of the two genes, according to long-term in vivo experiments or to experiments with primary cultures of zona glomerulosa cells. Expression of the non-aldosterone-producing enzyme is induced by ACTH, whereas the expression of the aldosterone-producing enzyme is dependent on the extracellular potassium concentration.