ZONA GLOMERULOSA-SPECIFIC FACTOR - CLONING AND FUNCTION

The rat adrenal cortex is composed of three zones: the zona glomerulos a, the zona fasciculata, and the zona reticularis. Several investigato rs have claimed the presence of a zona intermedia between the zonae gl omerulosa and fasciculata. The cells of zona glomerulosa, a few layers of cells just beneath the adrenal capsule, synthesize and secrete ald osterone, whereas those of zonae fasciculata and reticularis secrete g lucocorticoids and androgens, respectively. The function of the cells in zona intermedia is unclear, because they express neither aldosteron e synthase nor II beta-hydroxylase. To investigate the mechanism under lying the zonal differentiation of adrenocortical steroidogenesis, att empts have been made to isolate and characterize zone-specifically exp ressed proteins such as steroidogenic enzymes and putative regulatory factors. Having subtracted the mRNAs present in the decapsulated adren al gland fr-om those in the adrenal capsule, we successfully isolated three distinct clones, each specifically expressed in the zona glomeru losa. One clone encoded a protein named zona glomerulosa-specific fact or (ZOG), which had a putative signal peptide at the N-terminus, six t andem epidermal growth factor (EGF)-like repeats, and a transmembrane domain in the central portion and a short cytosolic stretch at the C-t erminus. Immunohistochemical studies using the antibody raised against ZOG confirmed the presence of the protein in all layers of cells in t he zona glomerulosa. In contrast, cells possessing aldosterone synthas e were present only in the periphery of zona glomerulosa, just beneath the capsule. These findings suggest that there are at least two kinds of zona glomerulosa cells in the rat adrenal cortex, one expressing a ldosterone synthase as well as ZOG, and another expressing only ZOG. T he cells in the zona intermedia did not express ZOG, aldosterone synth ase, or II beta-hydroxylase, but did express Ad4BP. ZOG was nor detect ed in zonae fasciculata and reticularis where II beta-hydroxylase was present. (C) 1997 by Elsevier Science Inc.