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 alpha 1- and beta 1-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 alpha 1- and beta 1-mRNA after glucocorticoids. The alpha 1- and beta 1-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 alpha 1-promoter was studied by gel retardation assay. Nuclear protein from glucocorticoid-treated rats retarded a fragment of alpha 1-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 alpha 1-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 alpha 1- and beta 1-Na(+)-K(+)-ATPase subunits. It is likely that the binding of glucocorticoid receptor to alpha 1-Na(+)-K(+)-ATPase promoter requires the presence of an auxiliary factor.
Wang
Z M
ZM
Pediatric Unit, Karolinska Institute, St. Göran's Children's Hospital, Stockholm, Sweden.
Yasui
M
M
Celsi
G
G
D000818:Animals; D000831:Animals, Newborn; D001623:Betamethasone / Q000494:pharmacology; D015152:Blotting, Northern; D003513:Cycloheximide / Q000494:pharmacology; D005938:Glucocorticoids / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology / Q000502:physiology*; D008297:Male; D009687:Nuclear Proteins / Q000502:physiology; D011401:Promoter Regions, Genetic; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*
D005938:Glucocorticoids; D009687:Nuclear Proteins; D001623:Betamethasone; D003513:Cycloheximide; D000254:Sodium-Potassium-Exchanging ATPase