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

哺乳动物的肾上腺皮质包含三个不同的区域，合成不同的类固醇激素。我们以前发现了一个假定的干细胞区之间的小球和束状。最近，我们建立了未分化的肾上腺皮质细胞系能够分化的刺激。由于预期这种未分化细胞表达在功能分化中起重要作用的分子，我们试图克隆在未分化细胞中特异性表达的cDNA。当进行消减克隆时，分离出编码新分泌蛋白的cDNA。编码的蛋白质由分泌信号、富含半胱氨酸的序列和无催化活性的组织蛋白酶B相关区域组成，命名为肾上腺皮质区带化因子-1（AZ-1）。mRNA水平分析显示，AZ-1的表达水平与肾上腺皮质细胞中类固醇11 β-羟化酶的表达水平呈负相关。组织化学检查显示AZ-1在外皮质细胞中合成，从其分泌，并且定位于肾上腺皮质实质细胞周围，这意味着AZ-1是细胞外基质的组分。这些结果提示AZ-1在决定肾上腺皮质细胞的带状分化中可能起作用

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