Analysis on the lineage of adrenocortical cells with 3-dimentional arrangement

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The adrenal cortex is composed of two functionally and ontogenetically different tissues, the medulla and the cortex. The cortex of mesodermal origin further separates into three concentric zones with specific functions : the zona glomerulosa(zG), the zona fasciculata (zF) and the zona reticularis (zR). Formerly we discovered another zone(undifferentiated cell zone : zU) between zG and zF ; cells in the layer are thought to be stem cells for adrenocortical cells as judged by their inability to express zone-specific steroidogenic enzymes and the behavior of proliferating cells around the zone. We then established such cell-lines(zU-cell line). We tried to transplant the zU cells to the kidney of scid mice, but so far we have not succeeded yet. This study was aimed to investigate the lineage of adrenocortical cells and mechanisms of the maintenance of cortical zones.A new secretory protein(designated later as adrenocortical zonation factor 1 : AZ-1) was identified in the cell line described above by subtractive hybridization. The protein contained a secretory signal, EGF-like repeats, and a proteolytically inactive catepsin B- related sequence. The AZ-1 mRNA was detected only in zU and zG. Interestingly the expression of AZ-1 mRNA in adrenocortical cells was inversely correlated with that of P45011β mRNA. AZ-1 protein, on the other hand, was observed in extracellular portions of whole drenal cortex ; it colocalizes with laminin, collagen, and fibronectin which associate with blood vessels. During development of the cortex, AZ-1 always colocalized with those extracellular matrix. The migration and differentiation of cortical cells may occur along extracellular matrix with the aid of AZ- I.