Phenotypic changes and proliferation of adrenocortical cells during adrenal regeneration in rats

Adrenal regeneration after enucleation includes both cell proliferation and differentiation, but the phenotype of the proliferating cell remains controversial. Immunoperoxidase localization of cytochrome P450 aldosterone synthase (P450aldo) and cytochrome P450 11β-hydroxylase (P45011β) and of Ki-67 was used to identify adrenocortical cell phenotypes and proliferating cells, respectively. Comparisons were made between regenerating and intact adrenals collected from rats on low or normal Na⁺ diets. During the first week after enucleation, P45011β was expressed reflecting the presence of fasciculata cells; however, P450aldo was detected only in adrenals from low Na⁺ rats. On normal and low Na⁺, glomerulosa cells were replaced by intermedia cells, whereas on low Na⁺, glomerulosa cells were replaced by fasciculata cells. Proliferation was observed only in glomerulosa and fasciculata, but not intermedia cells. These findings suggest that the expression of the glomerulosa cell phenotype is decreased in the early stages of adrenal regeneration, that differentiation from a glomerulosa to an intermediate or fasciculata cell phenotype is influenced by low Na⁺ and that glomerulosa and fasciculata cells proliferate in response to enucleation.