Zone-specific expression of aldosterone synthase cytochrome P-450 and cytochrome P-45011 beta in rat adrenal cortex: histochemical basis for the functional zonation.

Abstract

Zonal distribution of aldosterone synthase cytochrome P-450 and cytochrome P-45011 beta in rat adrenocortex was investigated immunochemically using specific antibodies to these enzymes. Localization of aldosterone synthase cytochrome P-450 (cytochrome P-450aldo), a recently identified enzyme that converts deoxycorticosterone to aldosterone in rat adrenocortex was strictly confined to two or three outermost cell layers in the zona glomerulosa. In contrast, cytochrome P-45011 beta, which forms corticosterone, but not aldosterone, from deoxycorticosterone, was localized in the zona fasciculata-reticularis and not in the zona glomerulosa. Neither enzyme was detected in the medulla or the capsule. The functional zonation of adrenocortex with respect to aldosterone and corticosterone syntheses is, thus, ascribable to the localization of cytochromes P-450aldo and P-45011 beta in the respective zones. When rats were maintained under Na-depleted conditions for 10 days, the zona glomerulosa cells containing cytochrome P-450aldo proliferated to 10-15 layers, the thickness of which was 5-7-fold that in the nonstimulated rats. Proliferation of the cytochrome P-450aldo-positive cells into the zona fasciculata-reticularis was also observed along with arterial walls. Under these conditions, no significant change in the distribution of cytochrome P-45011 beta was noted. These results indicate that the angiotensin-II stimuli, which had been elicited by the low Na treatment, promoted proliferation of the glomerulosa cells, resulting in increased expression of cytochrome P-450aldo in rat adrenocortex.

The transcriptional regulating protein of 132 kDa (TReP-132) differentially influences steroidogenic pathways in human adrenal NCI-H295 cells

“…By contrast, the transitional zone formation, which leads to the zonae fasciculata and reticularis, is associated with increased levels of the P450c17 enzyme (Mesiano & Jaffe 1997). As well, P450c11 aldo and P450aro expression is specific to the zonae glomerulosa and reticularis, respectively (Malee & Mellon 1991, Ogishima et al 1992. Thus, the ability of TReP-132 to increase transcription of P450c17 and P450aro in contrast to the weak effect on 3 -HSDII and P450c11aldo in NCI-H295 cells, raises the possibility that TReP-132 represents a marker of the zonae fasciculata and reticularis cell phenotype during fetal adrenal development.…”

“…Following the conversion of Preg to Prog by 3 -HSDII, Prog is a substrate of both the P450c17 and P450c21 enzymes, and thus represents a second branch-point towards either the mineralocorticoid or glucocorticoid pathways. Moreover, the expression of genes encoding P450aro, P450c11aldo and P450c11 is specific to each adrenal zone (Malee & Mellon 1991, Ogishima et al 1992. Hence, the control of adrenal steroidogenic pathways requires a coordinated transcriptional regulation of genes encoding these key enzymes.…”

Very low-density lipoprotein (VLDL)-induced signals mediating aldosterone production

“…Progesterone is then hydroxylated to deoxycorticosterone by CYP21 and is converted to aldosterone by three oxidation reactions: an 11 beta-and 18-hydroxylation, followed by an 18-oxidation, which are catalyzed by aldosterone synthase CYP11B2 (in humans). The expression of CYP11B2 occurs only in the zona glomerulosa, which prevents aldosterone production in the other adrenocortical zones, the zona fasciculata and the zona reticularis (Domalik et al 1991, Ogishima et al 1992, LeHoux et al 1995, Pascoe et al 1995. Thus, aldosterone production involves two key steps: the first (acute) rate-limiting step requires the expression and activity of the steroidogenic acute regulatory (StAR) Figure 1 Steroidogenesis in the adrenal cortex.…”

Localization and Differential Expression of Adenylyl Cyclase Messenger Ribonucleic Acids in Rat Adrenal Gland Determined by in Situ Hybridization*

“…To study the effect of sodium depletion, adult male rats, weighing 150 g, were divided in two groups: the control group that received a synthetic diet containing a normal amount of Na (86 mmol/kg), and a sodium-restricted group that received a synthetic diet containing a low (8.6 mmol/kg) amount of Na for 9 days as described previously (21,22). Male and female rat pups were killed on postnatal days 1 (PN1) and 7 (PN7), and males were killed at postnatal 21 (PN21) and 90 (PN90) days of age for the developmental study.…”

“…The specificity of steroid biosynthesis to different zones of the adrenal cortex is due to the presence of two highly homologous cytochromes: CYP11B2, which is responsible for the synthesis of aldosterone in the zona glomerulosa, and CYP11B1, which is responsible for the synthesis of corticosterone in the zonae fasciculata-reticularis (6,22,30). Dietary sodium restriction is known to induce the proliferation of the glomerulosa cells and to increase the mRNA level of CYP11B2.…”