Implication of ZOG protein (zona glomerulosa-specific protein) in zone development of the adrenal cortex.

The three zones of adrenal cortex are thought to arise from a single multipotential stem cell. Immunohistochemical studies of fetal and adult adrenals using an antibody against a previously-cloned ZOG protein, a rat homolog of Pref-1, were conducted to explore its roles in the differentiation of cortical tissues. At the early embryonic stage, ZOG was already expressed in adrenogonadal primordial cells. The ZOG-positive cells gradually formed the adrenal primordium by E14.5. By E17.5 the expression was repressed in the inner part of the aggregate and these cells began to express CYP11B1. The ZOG-positive cells at this stage existed at the periphery of the aggregate but they did not express CYP11B2 yet. Not until E20.5 did the aldosteronogenic cells appear among the ZOG-positive cells at the outermost part of the gland. Based on these and the other findings the zonal development of the adrenal cortex is discussed.

New insights into zonal differentiation of adrenal autotransplants in the rat: an immunohistochemical study.

Adrenal gland autotransplantation, an interesting model of adrenal regeneration, provides the reconstruction of distinct functional and morphological zonae. An immunohistochemical study of the adrenal gland of adult male rats after autotransplantation and endothelin-1 (ET-1) stimulation was carried out. The technique involved total adrenalectomy and immediate autotransplantation of small adrenal pieces under the skin of the dorsal region. The animals were killed 90 days after the autotransplantation and 1 h after intravenous ET-1 administration. Sections of recovered adrenal grafts were incubated with IZAb, a monoclonal antibody which interacts with an antigen (IZAg) predominantly found in rat adrenal inner zones. Saline-treated control autotransplanted animals showed IZAb immunostaining in almost all adrenocortical tissue, with the exception of small clusters of cells beneath the capsule. ET-1-treated animals exhibited an extended zone devoid of immunostaining and located in the subcapsular area. In addition, ET-1-stimulated animals showed significant increases in aldosterone as well as corticosterone concentrations in plasma. These results revealed that ET-1 stimulated the development of an extended subcapsular zone lacking IZAg expression, an effect that suggests its role in zona glomerulosa induction in these animals.

The development of the adrenal cortex in the rat. An immunohistochemical study.

The Inner Zone Antibody (IZAb) is a monoclonal antibody which interacts with an antigen found predominantly in rat adrenal inner cortical zones. Since its expression increases after ACTH treatment the antigen may have a role in steroidogenesis although, so far, this has not yet been fully characterised. Due to its molecular weight, it cannot be any of the known cytochrome P450 proteins. In this study we examined the expression of IZAb in male and female rats throughout their postnatal development and in aged animals. In a different set of animals, blood was collected for hormonal assays and the adrenals stained with classical methods. The staining with IZAb was clear from the first post-natal day. The zona glomerulosa which was always present at birth, was easily distinguished and unstained. The staining in the inner zone cells was fainter at birth and increased progressively until postnatal day 20. Afterwards these cells were remarkably stained at all ages. Medullary cells were also present from birth although they were generally found in clusters instead of constituting a well defined zone. Cortical cells appeared in the medullary zone at all ages after its complete development. The zona glomerulosa increased in size until approximately postnatal day 40 while the inner zones increased until day 70. The area of the cortex was significantly different between the two sexes from day 50 onwards and this was predominantly due to differences in the zona fasciculata. Corticosterone levels increased until approximately day 25 in the male rat and until day 45 in the female.(ABSTRACT TRUNCATED AT 250 WORDS)

Distribution of the adrenocortical inner zone antigen.

Previous studies using a mouse monoclonal antibody (IZAb) have identified inner zone-specific antigens (IZAg 1 and 2) in the rat adrenal cortex. The expression of IZAg1 is enhanced by dibutyryl-cyclic AMP or ACTH in vitro and by in vivo ACTH treatment. These studies also suggest that IZAg may be involved in steriogenesis in rat adrenals. Using sensitive detection methods, the distribution of IZAg in adrenals from other species and in other rat tissues was studied. Pig and rabbit adrenals expressed an IZAb-immunoreactive protein with molecular mass identical with that of IZAg1, but no immunoreactivity was detected in bovine, guinea-pig or mouse adrenals. In the rabbit adrenal, as in the rat, IZAb bound only to zonae fasciculata/reticularis cells. However, the whole adrenal cortex in the pig immunoreacted with IZAb. Although immunofluorescence was observed in human adrenal sections, predominantly in the zona reticularis, no significant immunoreactive protein band was detected by immunoblot analysis. Apart from the zonae fasciculata/reticularis in the adrenal gland, an IZAb-immunoreactive protein with a molecular mass of 26,000 Da, corresponding to IZAg1, was also found in rat hepatocytes, renal tubules, ovary (corpus luteum, interstitial cells, theca interna of mature follicles) and Leydig cells. The observations suggest that IZAg may be involved in the processes of biosynthesis, metabolism and/or excretion of steroid hormones.