A novel secretory protein identified from an adrenocortical precursor cell-line

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Mammalian adrenal corteces contain three distinct zones which synthesize different steroid hormones. We previously found a putative stem cell zone between the zona glomerulosa and the fasciculata. Recently, we established undifferentiated adrenocortical cell lines capable of differentiating upon stimuli. As it was expected that such undifferentiated cells express molecules that play an important role in the functional differentiation, we attempted to clone cDNAs that were expressed specifically in the undifferentiated cells. When a subtractive cloning was performed, a cDNA encoding a novel secretory protein was isolated. The encoded protein was composed of a secretory signal, cysteine-rich sequences, and a catalytically inactive cathepsin B-related region, and it was named adrenocortical zonation factor-1 (AZ-1). Analysis of mRNA levels showed that expression levels of AZ-1 were inversely correlated with that of steroid 11beta-hydroxylase in adrenocortical cells. Histochemical examinations revealed that AZ-1 was synthesized in the outer cortical cells, secreted therefrom, and localized around adrenocortical parenchymal cells, implying that AZ-1 was a component of extracellular matrix. These results suggest a putative role of AZ-1 in determining the zonal differentiation of adrenocortical cells