Subcellular localization of glucocorticoid receptor protein in the human kidney glomerulus

Background. The detailed mechanisms of glucocorticoid action in idiopathic nephrotic syndrome and progressive glomerulonephritides have not been clear ly elucidated. The pharmacological actions of glucocorticoids are mediated by their binding to an intracellular protein, the glucocorticoid receptor ( GR). The: determination of GR localization in normal glomerular cells is es sential to elucidate the mechanisms of glucocorticoid action in various glo merular diseases. Methods. We carried out an immunoblot examination using antihuman GR-specif ic antibody and homogenates of isolated normal human glomeruli and mesangia l cells in culture. Immunohistochemical examinations were also performed on normal human kidney specimens at light and electron microscopic levels. Th e nuclear translocation of GRs elicited by ligand binding was further inves tigated by confocal laser-scanning microscopic inspection of freshly isolat ed glomeruli and mesangial cells cultured with dexamethasone. Results. An immunoblot examination demonstrated the presence of a 94 kDa pr otein, a molecular weight consistent with that of GRs, in the homogenates o f glomeruli and cultured mesangial cells. By light microscopic examination, GRs were strongly detected in the nucleus and moderately in the cytoplasm of all glomerular cells, parietal and visceral epithelial cells, endothelia l cells, and mesangial cells. By electron microscopic examination, the nucl ear GRs of all glomerular cells were found to be diffusely distributed in t he euchromatin. Additionally, the immunofluorescence intensities of nuclear GRs in isolated glomeruli and mesangial cells in culture became more inten se by the addition of dexamethasone. Conclusions. Our findings suggest that all subsets of human glomerular cell s definitely express the GR protein, which potentially undergoes translocat ion by glucocorticoids.