Development of aldosterone biosynthesis during fetal and pediatric periods; Histological analysis of CYP11B2-positive cell distribution in the zona glomerulosa of human adrenal

The distribution of CYP11B2-positive or aldosterone producing adrenocortical cells in human fetuses and children and their age-dependent changes has not been studied. We aimed to explore the changes of aldosterone biosynthesis and age-related histological alterations of the zona glomerulosa in human adrenal gland during fetal and pediatric periods. We first reviewed 125 fetal and pediatric autopsy cases and retrieved 78 adrenals from 70 cases. CYP11B2 immunohistochemistry and quantitative image analysis of its results were performed in all adrenal glands. The ratio of the definitive zone (DZ) or zona glomerulosa (ZG) / the whole adrenocortical areas started to increase in the 2nd trimester, subsequently decreased in the 3rd, increased after birth, peaked in infancy, and then gradually decreased. The ratio of CYP11B2-positive / whole adrenocortical areas remained low during the fetal period but increased after birth, peaked at infancy, and then decreased. The ratio of CYP11B2-positive / DZ or ZG areas and CYP11B2-positive areas / depth of DZ or ZG demonstrated a distinctive bimodal pattern, with one peak in the fetal period and another in the neonatal period to infancy. This is the first study to perform quantitative analysis of the distribution of CYP11B2-positive cells, the histological DZ or ZG, and the development of aldosterone biosynthesis in human adrenal glands during fetal and pediatric periods. •CYP11B2-positive cells became discernible in the DZ from 15 WG.•CYP11B2-positive cells gradually increased from around 21-23 WG.•After birth, CYP11B2-positive cells were detected in the ZG along with the development of permanent adrenal cortex.