Age- and tissue-specific induction of NHE3 by glucocorticoids in the rat small intestine

Of the two known apical isoforms of the Na⁺/H⁺ exchanger (NHE) family, only the NHE3 gene is regulated by glucocorticoids. The aim of these studies was to investigate the mechanisms underlying the effects of methylprednisolone (MP) on expression of NHE3 in the proximal and distal small intestine of suckling and adult rats. Immunoblots showed that the glucocorticoid responsiveness in the proximal small intestine was greatest in suckling animals (NHE3/β-actin: 0.43 ± 0.09 control vs. 1.57 ± 0.15 MP; P < 0.001), and responsiveness decreased with age with no effect in adults (0.56 ± 0.14 vs. 0.64 ± 0.17). Distal small intestine was responsive only in adult rats (0.49 ± 0.13 vs. 1.65 ± 0.09; P < 0.001). This pattern was confirmed at the mRNA level and by ²²Na⁺ uptake. Western blot and [³H]dexamethasone mesylate binding showed that the responsiveness of NHE3 to glucocorticoids is directly related to the expression of glucocorticoid receptor (GR) in the small intestine. These studies suggest that loss and gain of glucocorticoid responsiveness in the proximal and distal small intestine, respectively, are related to age- and segment-dependent expression of GR.