Glucocorticoids differentially regulate the mRNA for Na+,K(+)-ATPase isoforms in infant rat heart.
The postnatal maturation of Na+,K(+)-ATPase alpha- and beta-subunit genes can be accelerated in the rat kidney by the administration of glucocorticoid hormones (GC). In heart, Na+,K(+)-ATPase alpha-isoform and beta-subunit genes exhibit a complex pattern of expression during development. This study examines the role of GC in the regulation of Na+,K(+)-ATPase mRNA abundance in rat heart during infancy. In 10-d-old rats given injections with a single intraperitoneal dose of betamethasone or diluent, the Na+,K(+)-ATPase activity was 2-fold higher in treated than in control rats after 24 h. GC differentially regulated the mRNA for Na+,K(+)-ATPase subunits. A significant increase in Na+,K(+)-ATPase mRNA occurred with a dose of 2.5 micrograms betamethasone/100 g body weight. The following experiments were performed with a saturating dose of 60 micrograms betamethasone/100 g body weight. The alpha 1 mRNA was moderately but significantly increased (1.5-fold) 6 h after treatment. The mRNA for the alpha 2 subunit increased 2.2-fold after betamethasone treatment. The mRNA for beta 1 was numerically increased after 20 min (1.3-fold); it was 1.5-fold higher (p < 0.05) after 1 h and was 3-fold higher after 6 h (p < 0.01). Betamethasone treatment did not significantly change the abundance of the mRNA for the alpha 3 subunit. The expression of actin mRNA was not altered after GC. These data indicate that GC hormones may act as a "molecular switch" in the developmental expression of the mRNA for the Na+,K(+)-ATPase alpha-isoforms and contribute in stimulating the maturation of rat heart during the preweaning period.
Department of Pediatrics, St. Göran's Children's Hospital, Karolinska Institutet, Stockholm, Sweden.
Z M
ZM
Wang
G
G
Celsi
D000818:Animals; D000833:Animals, Suckling; D001623:Betamethasone / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000254:growth & development; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
D007527:Isoenzymes; D012333:RNA, Messenger; D001623:Betamethasone; D000254:Sodium-Potassium-Exchanging ATPase