Adrenal androgen synthesizing type 5 17β-hydroxysteroid dehydrogenase (HSD17B5 or AKR1C3 as listed in the Hugo Database) was almost confined to ZR of human adrenals throughout development. The number of BCL2-positive cells increased in ZR and decreased in ZF during development. Results demonstrated that proliferative adrenocortical cells were predominantly detected in the zona glomerulosa and partly in outer zona fasciculata (ZF) before 4 years of age and in ZR after 4 years of age, but the number of these cells markedly decreased around 20 years of age. We further evaluated immunoreactivity of both KI67 and BCL2 in order to clarify the equilibrium between cell proliferation and apoptosis in the homeostasis of developing human adrenals. Results demonstrated that ZR became discernible around 4 years of age, and both thickness and ratio per total cortex of ZR increased in an age-dependent fashion thereafter, although there was no significant increment in total thickness of developing adrenal cortex.

Therefore, in this study, 44 human young adrenal autopsy specimens retrieved from large archival files ( n=252) were examined for immunohistochemical and morphometric analyses. Age-related morphologic development of human adrenal zona reticularis (ZR) has not been well examined.

Zona fasciculata