Effects of Short‐Term and Long‐Term Dexamethasone Action on Expression of Glucocorticoid and Mineralocorticoid Receptors in the Gastric Mucosa

Abstract

Glucocorticoids may have dual action on the stomach: gastroprotective and proulcerogenic one. Our previous study was designed to investigate how physiological gastroprotective action of glucocorticoids can be transformed to pathological ulcerogenic effect. The results obtained demonstrate that single injection of dexamethasone at the dose of 1 mg/kg may attenuate or aggravate indomethacin‐induced gastric erosions depending on the time of its injection before indomethacin (prolongation of dexamethasone action). At the present study to elucidate the mechanisms of transformation of gastroprotective action of dexamethasone into ulcerogenic one we tested the hypothesis that disbalance between the glucocorticoid and mineralocorticoid receptors (GR and MR) may contribute to this transformation. To test the hypothesis, effect ща dexamethasone at the dose of 1 mg /kg, (i.p.) on the expression of GR and MR in the gastric mucosa was studied 1 h (a short‐term action when the gastroprotective action was observed) and 24 h (long‐term action when the proulcerogenic effect was observed) after its administration. The expression of GR and MR was detected by a immunohistochemical staining technique using α‐glucocorticoid (ab3580; 1:500. Abcam) and mineralоcorticoid (ab41912; 1:500. Abcam) receptor antibodies. The results of the staining were assessed by a morphometric study of microscopic images in five fields of view using the ImajeJ software. A distribution of cytoplasmic staining was estimated with relative stained area (%) in gastric glands and smooth muscle cells of muscularis mucosae. We found that GR are presented in the parietal cells, whereas MR are ubiquitous. Dexamethasone provoked translocation of both GR and MR into nuclei. The short‐term effect of dexamethasone resulted in a decrease of cytoplasmic GR and their translocation into the cell nuclei. The long‐term dexamethasone exposure increased cytoplasmic GR expression not accompanied by nuclear translocation. The short‐term dexamethasone action caused an increase of cytoplasmic MR level, but did not lead to nuclear translocation of these receptors. The long‐term action of dexamethasone induced nuclear translocation of MR, without significant changes of MR expression in cytoplasm. The results suggest that disbalance between GR and MR may contribute to transformation of gastroprotective action of dexamethasone to proulcerogenic effect and support the hypothesis.Support or Funding InformationThe study was supported by grant of Russian Science Foundation (RSF) N 14‐15‐00790.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.