Effects of prolonged infusion of basic fibroblast growth factor and IGF-I on adrenocortical differentiation in the autotransplanted adrenal: an immunohistochemical study

Adrenocortical regeneration after adrenal autotransplantation provides a mo del for the study of local autocrine/paracrine mechanisms involved in the g rowth and differentiation of the adrenal cortex. To study the possible invo lvement 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 adrena l autotransplants in adult male rats. To distinguish between fasciculata an d glomerulosa-like cells with accuracy, tissue sections were immunostained with IZAb, which recognizes the inner zone antigen (IZAg present in fascicu lata 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, ult rastructural examination showed cells containing mitochondria with irregula r cristae resembling those of the fetal or immature glomerulosa cells. In c ontrast, no significant morphological differences were observed in bFGF-tre ated 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. Plasm a aldosterone and corticosterone concentrations were lower in autotransplan ted control animals than in intact controls, although plasma renin activiti es were similar. IGF-I treatment significantly increased aldosterone concen trations, whereas corticosterone and plasma renin activity were reduced. bF GF infusion further reduced plasma aldosterone, although plasma renin activ ity 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 glomerulos a function, appears partly to replicate the actions of ACTH in normal anima ls. In contrast, IGF-I enhances the glomerulosa secreting phenotype and dim inishes that of the fasciculata/ reticularis, possibly replicating the acti ons of angiotensin II or a low sodium diet.