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P Vendeira, D Pignatelli, D Neves, MM Magalhaes, MC Magalhaes and GP Vinson

Adrenocortical regeneration after adrenal autotransplantation provides a model for the study of local autocrine/paracrine mechanisms involved in the growth and differentiation of the adrenal cortex. To study the possible involvement of some growth factors, namely basic fibroblast growth factor (bFGF, FGF-2) and insulin-like growth factor I (IGF-I), in cell differentiation, immunohistochemical and ultrastructural studies were carried out on adrenal autotransplants in adult male rats. To distinguish between fasciculata and glomerulosa-like cells with accuracy, tissue sections were immunostained with IZAb, which recognizes the inner zone antigen (IZAg) present in fasciculata and reticularis cells but absent from the glomerulosa, and by electron microscopy. IGF-I-treated animals exhibited a clear glomerulosa-like zone that was devoid of IZAb immunostaining. In this outer subcapsular area, ultrastructural examination showed cells containing mitochondria with irregular cristae resembling those of the fetal or immature glomerulosa cells. In contrast, no significant morphological differences were observed in bFGF-treated animals when compared with those from saline-treated controls, in both of which, IZAb immunostaining occurred in almost all adrenocortical cells, with no clear zonation or glomerulosa, as seen in the intact animal. Plasma aldosterone and corticosterone concentrations were lower in autotransplanted control animals than in intact controls, although plasma renin activities were similar. IGF-I treatment significantly increased aldosterone concentrations, whereas corticosterone and plasma renin activity were reduced. bFGF infusion further reduced plasma aldosterone, although plasma renin activity and corticosterone were unaffected. These results suggest that the two growth factors have different effects on zonal differentiation and function in the autotransplanted gland. In particular, bFGF, by reducing glomerulosa function, appears partly to replicate the actions of ACTH in normal animals. In contrast, IGF-I enhances the glomerulosa secreting phenotype and diminishes that of the fasciculata/reticularis, possibly replicating the actions of angiotensin II or a low sodium diet.

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P Vendeira, D Pignatelli, D Neves, M M Magalhães, M C Magalhães, M M Ho and G P Vinson

Abstract

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.

Journal of Endocrinology (1996) 149, 497–502