Glucocorticoids regulate the transcription of Na⁺-K⁺-ATPase genes in the infant rat kidney

Glucocorticoids modulate the maturation of Na⁺-K⁺-ATPase mRNA in a tissue- and age-dependent manner. In this study, we report the effect of glucocorticoids on Na⁺-K⁺-ATPase gene transcription in the infant rat kidney. Ten-day-old rats were treated with one intraperitoneal injection of betamethasone. In glucocorticoid-treated rats, there was a significant increase in renal cortical α₁- and β₁-mRNAs (3.08 ± 0.34- and 4.06 ± 0.10-fold). Pretreatment with cycloheximide, an inhibitor of protein synthesis, did not abolish the increase in α₁- and β₁-mRNA after glucocorticoids. The α₁- and β₁-gene transcription rates were significantly increased in nuclei isolated from kidneys of glucocorticoid- treated rat (2.16 ± 0.05- and 3.12 ± 0.50-fold). Interaction between nuclear proteins and Na⁺-K⁺-ATPase α₁-promoter was studied by gel retardation assay. Nuclear protein from glucocorticoid-treated rats retarded a fragment of α₁-promoter that includes a half-consensus glucocorticoid response element (GRE) at position -750 bp but did not retard a fragment including a half-consensus GRE at position -481. Retardation of α₁- promoter was inhibited by incubation with molar excess of GRE or with a monoclonal antibody against glucocorticoid receptor. We conclude that in the infant kidney, glucocorticoids directly stimulate the transcription of α₁- and β₁-Na⁺-K⁺-ATPase subunits. It is likely that the binding of glucocorticoid receptor to α₁-Na⁺-K⁺-ATPase promoter requires the presence of an auxiliary factor.