Ectopic localization of CYP11B1 and CYP11B2-expressing cells in the normal human adrenal gland

The sharp line of demarcation between zona glomerulosa (ZG) and zona fasciculata (ZF) has been recently challenged suggesting that this interface is no longer a compartment boundary. We have used immunohistochemical analyses to study the steroid 11β-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) pattern of expression and investigate the remodeling of the adrenal cortex in relation to aging. We analyzed human adrenal glands prepared from 47 kidney donors. No aldosterone-producing micronodules (APMs) were detectable in the younger donors aged between 22-39 but the functional ZG depicted by positive CYP11B2 staining demonstrated a lack of continuity. In contrast, the development of APMs was found in samples from individuals aged 40-70. Importantly, the progressive replacement of CYP11B2-expressing cells in the histological ZG by CYP11B1-expressing cells highlights the remodeling capacity of the adrenal cortex. In 70% of our samples, immunofluorescence studies revealed the presence of isolated or clusters of CYP11B2 positive cells in the ZF and zona reticularis. Our data emphasize that mineralocorticoid- and glucocorticoid-producing cells are distributed throughout the cortex and the medulla making the determination of the functional status of a cell or group of cells a unique tool in deciphering the changes occurring in adrenal gland particularly during aging. They also suggest that, in humans, steroidogenic cell phenotype defined by function is a stable feature and thus, the functional zonation might be not solely maintained by cell lineage conversion/migration.