Immunolocalization of gluco- and mineralocorticoid receptors in rabbit kidney

Abstract

The localization of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) was determined in the rabbit kidney by immunohistochemistry with the use of a monoclonal, anti-GR antibody and a monoclonal, anti-idiotypic, anti-MR antibody. Immunostaining was performed on serial histological sections from normal and adrenalectomized rabbits. The specificity of immunostaining was assessed for MR by in situ competition studies with steroids and for GR by presaturation of the antibody with GR preparation. Immunostaining by both the anti-MR and the anti-GR antibodies was present in all parts of the distal nephron (beyond proximal tubule) and absent in the glomerulus and proximal tubule. The absence of staining by the anti-GR antibody in the proximal tubule suggests that the effects of glucocorticoids in this structure involve either a GR different from that of distal structures or a non-receptor mediated mechanism of action. MR immunostaining predominates in the distal and all along the collecting tubule in its cortical, medullary, and papillary portions. GR immunostaining was most abundant in the medullary ascending limb and distal tubule. Immunostaining by both antibodies was present in papillary interstitial cells and cells of the epithelium lining the papilla. Fifteen to twenty percent of the cells of the cortical collecting tubule, presumably intercalated cells, were devoid of MR and GR immunostaining. Immunostaining was present in both nuclear and cytoplasmic cell compartments. No clear difference was observed between normal and adrenalectomized rabbits. This study is the first report on renal immunolocalization of GR compared with MR. In addition, we show evidence for new targets for corticosteroid hormones such as papillary interstitial cells and papillary epithelium.

Implication of the mineralocorticoid axis in rainbow trout osmoregulation during salinity acclimation

“…The localization of GR1 in the intestine shown in this study is in good agreement with the localization shown in tilapia (Oreochromis mossambicus) posterior intestine (Takahashi et al 2006a) and sea bass (Dicentrarchus labrax) intestine (Vazzana et al 2008). In agreement with these data obtained in fish, co-localization of GR and MR has previously been shown in the mammalian kidney and intestine (Farman et al 1991, Whorwood et al 1993.…”

In vivo nuclear translocation of mineralocorticoid and glucocorticoid receptors in rat kidney: differential effect of corticosteroids along the distal tubule

“…Immunohistochemical, hormone binding, and RT-PCR studies revealed the MR unambiguously along the ASDN (4,7,10,13,32,37,45,53), but MR localization in upstream nephron portions such as the thick ascending limb (TAL) is less clear. Similarly, a convincing demonstration of MR expression in intercalated cells in the kidney in vivo is lacking.…”

“…So far, only some expression data on immunoisolated cells from rabbit CD suggested the expression of the MR in principal cells and at least some subtypes of intercalated cells (40). However, immunohistochemical studies failed to detect MR in intercalated cells in the collecting system of rat kidneys (4,13). In addition to the ambiguities regarding the cellular distribution of MR and GR, little is known about the corticosteroiddependent regulation of MR and GR in the kidney in vivo.…”

Vasopressin potentiates mineralocorticoid selectivity by stimulating 11 beta hydroxysteroid deshydrogenase in rat collecting duct.

“…This, in turn, could modulate the intensity (and perhaps the nature) of the hormonal response. Since 11 dehydro-derivatives of natural glucocorticoids have negligible affinity for the GR (9), the consequence is that in addition to an enhancement of aldosterone binding to MR, 11-HSD activity is expected to dampen or even supress glucocorticoid effects via the GR in cells expressing both MR and GR, (such as those of the renal collecting duct) (7). Thus, any increase in 11-HSD activity due to AVP is likely to reduce, and any decrease enhance, glucocorticoid action in the cell.…”

“…Activation of the V2 pathway results in enhancement of osmotic water permeability and sodium reabsorption. Aldosterone and glucocorticoid hormones bind to intracellular receptors, the mineralocorticoid (MR) and the glucocorticoid (GR) receptors that are coexpressed in the collecting tubule (7), and act as transcription factors to modulate gene expression (8). It has been shown that aldosterone and glucocorticoid hormones display the same affinity for the mineralocorticoid receptor (9).…”