Human Adrenocortical Remodeling Leading to Aldosterone-Producing Cell Cluster Generation.

Koshiro Nishimoto,Ken Nakagawa,Shuji Mikami,Mototsugu Oya,Fumiko Mitani,Shinya Morita,Tsugio Seki,Takeo Kosaka,Kuniaki Mukai,Yuichiro Hayashi,Yasuaki Kabe,Ghaith Al-Eyd,Makoto Suematsu

doi:10.1155/2016/7834356

Abstract

Background. The immunohistochemical detection of aldosterone synthase (CYP11B2) and steroid 11β-hydroxylase (CYP11B1) has enabled the identification of aldosterone-producing cell clusters (APCCs) in the subcapsular portion of the human adult adrenal cortex. We hypothesized that adrenals have layered zonation in early postnatal stages and are remodeled to possess APCCs over time. Purposes. To investigate changes in human adrenocortical zonation with age. Methods. We retrospectively analyzed adrenal tissues prepared from 33 autopsied patients aged between 0 and 50 years. They were immunostained for CYP11B2 and CYP11B1. The percentage of APCC areas over the whole adrenal area (AA/WAA, %) and the number of APCCs (NOA, APCCs/mm2) were calculated by four examiners. Average values were used in statistical analyses. Results. Adrenals under 11 years old had layered zona glomerulosa (ZG) and zona fasciculata (ZF) without apparent APCCs. Some adrenals had an unstained (CYP11B2/CYP11B1-negative) layer between ZG and ZF, resembling the rat undifferentiated cell zone. Average AA/WAA and NOA correlated with age, suggesting that APCC development is associated with aging. Possible APCC-to-APA transitional lesions were incidentally identified in two adult adrenals. Conclusions. The adrenal cortex with layered zonation remodels to possess APCCs over time. APCC generation may be associated with hypertension in adults.

Highlights

Immunohistochemical detection of aldosterone synthase (CYP11B2) and steroid 11β-hydroxylase (CYP11B1: cortisol synthesizing enzyme) has enabled the identification of aldosterone-producing cell clusters (APCCs) in the subcapsular portion of the normal human adrenal cortex
APCCs are indistinguishable from the normal adrenal cortex on hematoxylin-eosin- (H&E-) stained adrenal sections because APCCs consist of subcapsular zona glomerulosa- (ZG-) like cells and inner zona fasciculata- (ZF-) like cells
APCCs are distinct from aldosterone-producing adenomas (APAs), which cause primary aldosteronism (PA), in the following aspects [1, 2]: (i) APCCs are approximately 0.2–1.5 mm in length, whereas APAs are more than ∼3 mm in length. (ii) APCCs appear histologically normal in H&E staining with ZG- and ZF-like cells, whereas APAs consist of heterogeneous cells. (iii) APCCs express CYP11B2, but not CYP11B1, whereas APAs consist of heterogeneous tumor cells expressing either CYP11B2 or CYP11B1

Summary

Introduction

Immunohistochemical detection of aldosterone synthase (CYP11B2) and steroid 11β-hydroxylase (CYP11B1: cortisol synthesizing enzyme) has enabled the identification of aldosterone-producing cell clusters (APCCs) in the subcapsular portion of the normal human adrenal cortex. Previous studies demonstrated that APAs frequently harbor a somatic mutation in one of the 4 ion channel/pump genes (APA-associated mutations) including the potassium channel, inwardly rectifying subfamily J, member 5 (KCNJ5) [3] These mutations are considered to cause autonomous aldosterone production by triggering cellular depolarization and/or increasing intracellular calcium concentrations. The immunohistochemical detection of aldosterone synthase (CYP11B2) and steroid 11β-hydroxylase (CYP11B1) has enabled the identification of aldosterone-producing cell clusters (APCCs) in the subcapsular portion of the human adult adrenal cortex.

Methods

Results

Discussion

Conclusion