OR08-03 Ectopic Localization Of CYP11B1 and CYP11B2-Expressing Cells In The Normal Human Adrenal Gland

Abstract

Abstract Disclosure: C. Duparc: None. P. Camponova: None. M. Roy: None. H. Lefebvre: None. M. Thomas: None. The zonation of the human adrenal cortex has long been established morphologically and histologically as three distinct layers of cells. The outer zona glomerulosa (ZG) comprises densely packed cells arranged in clusters that produce aldosterone; the zona fasciculata (ZF) is composed of cells with large cytoplasm, containing lipid droplets arranged in radial columns that synthetize cortisol; and the zona reticularis (ZR) is composed of compact and pigmented cells producing androgens. The sharp line of demarcation between ZG and 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 (18 females, 29 males, ranging in age from 22 to 81 years old). 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. None of the 47 adrenals studied had a continuous CYP11B2 expression which appeared to be fragmented within the subcapsular region. Importantly, the progressive replacement of CYP11B2-expressing cells in the histological ZG by CYP11B1-expressing cells highlights the remodeling capacity of the adrenal cortex. Cells expressing respectively CYP11B1 and CYP11B2 were found interwoven at different levels: i) single or cluster of CYP11B2 cells can be observed in the inner cortex surrounded by CYP11B1-expressing cells (33/47, 70.21%) and ii) the two type of cells might be found in the same nest or basket of cells beneath the capsule (40/47 donors, 85.10%). Interestingly, CYP11B1 and CYP11B2 cells were also present within the ZR. Proliferation detected by Ki-67 expression occurred in 14.04% (±1.69%) of the CYP11B2-expressing cells while it appeared expressed in 85.96% (±1.69%) of the CYP11B1-positive cells (p<0.001). No significant correlation between Ki-67 and age or sex has been found. 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. Despite the fact that our data cannot exclude the existence of the CYP11B2+ cell conversion/migration lineage as demonstrated in mice they suggest that alternative mechanisms may exist in the human adrenal such as inward displacement of CYP11B2 expressing cells without lineage conversion. Presentation: Friday, June 16, 2023