Development of functional zonation in the rat adrenal cortex

In an attempt to elucidate the mechanism(s) through which the functional ad renal cortex is established, we analyzed immunohistochemically the expressi on of various markers for the adrenocortical zones, i.e. the zona glomerulo sa (zG), the zona fasciculata (zF), and the zona reticularis (zR), as well as markers for the medulla, and further examined the distribution and behav ior of DNA-synthesizing cells in rat adrenal glands during development. The results showed that 1) separation of the cortex and medulla, and the devel opment of functional zonation in the cortex began at around the time of bir th, 2) at fetal stages when cortical zonation was not established, DNA-synt hesizing cells were found scattered throughout the gland, where they prolif erated without significant migration, and 3) after birth in the adrenal cor tex with established cortical zonation, DNA-synthesizing cells were localiz ed near the undifferentiated zone between zG and zF, and then they migrated centripetally. Cell death appeared to occur in the innermost portion of th e cortex, where many resident macrophages are present. These findings illus trate basic processes underlying adrenal development and suggest that the u ndifferentiated region is apparently the stem cell zone of the adrenal cort ex that maintains the cortical zonation.