Steroid monooxygenases as markers for studying functional zonation in the adrenal cortex

Abstract

Aldosterone synthase cytochrome P450 ( P450aldo) and corticosteroid 11β hydroxylase ( P45011β) are the monooxygenases which localize in the zona glomerulosa and the zonae fasciculata–reticularis of the adrenal cortex, respectively. The former enzyme catalyzes the formation of the strongest mineralocorticoid, aldosterone, and the latter synthesizes the two major glucocorticoids, corticosterone and cortisol, from their respective precursors. Employing these two monooxygenases as markers for each adrenocortical zone, we investigated the molecular basis for the functional zonation and developmental processes of rat adrenal cortex. The results indicated that the specific function of each zone in rats as well as in humans is attributable to the expression of three monooxygenases, P450aldo, P45011β and steroid 17α-hydroxylase ( P45017α,lyase) in the component cells. This is in contrast with the fact that the specific functions of the zona glomerulosa and the zona fasciculata are determined by a protein–protein interaction between P450scc and P45011β in bovine adrenal cortex [S. Ikushiro et al., J. Biol. Chem. 267 (1992) 1464]. Furthermore, we found the presence of the fourth zone between the zona glomerulosa and the zona fasciculata in rat adrenal cortex and named it the undifferentiated cell zone; it turned out to be the stem cell zone which replenishes cells to each zone of adult rat adrenal cortex. Analyses of the developmental processes from fetal to adulthood and of the regeneration process of the enucleated adrenal cortex were also described.