Sensitive periods for glucocorticoids' regulation of Na+,K(+)-ATPase mRNA in the developing lung and kidney.
We have previously reported that in the infant rat renal cortex, a saturating dose of glucocorticoid hormones (GC) rapidly increases the abundance of Na+,K(+)-ATPase mRNA. We now show that this effect is dose dependent. In the renal cortex of 10-d-old rats, an increase in renal Na+,K(+)-ATPase mRNA occurs with 2.5 micrograms betamethasone/100 g body weight. In subsequent experiments, performed 6 h after a saturating dose (60 micrograms/100 g body weight), we show that the effect is age dependent. The most marked effects on renal cortical alpha-mRNA were found at 10 d of age (5.3- +/- 0.9-fold). A significant increase was also found in 20-d-old rats (1.6- +/- 0.2-fold), but no effect was found in fetal and 5-d-old rats. Studies were also performed on the lung, where the most marked effect was noted in the perinatal period (2.0- +/- 0.1-fold 2 d before birth and 1.76 +/- 0.2 at 5 d of age), but no effect on alpha-mRNA was found at 10 and 20 d. In one protocol, the effect of betamethasone on renal Na+K(+)-ATPase mRNAs abundance was determined in adult adrenalectomized rats. In these rats, betamethasone induced a significant 1.6- +/- 0.2-fold and 1.8- +/- 0.3-fold increase in renal Na+,K(+)-ATPase mRNA. This effect, however, was significantly smaller than the increase induced in intact 10-d-old rats. GC induction of Na+,K(+)-ATPase mRNA is age and tissue dependent and is dependent on factors other than GC-receptor availability. The GC-sensitive period appears to coincide with the physiologic need for organ maturation.
Department of Pediatrics, St. Göran's Children's Hospital, Stockholm, Sweden.
G
G
Celsi
Z M
ZM
Wang
G
G
Akusjärvi
A
A
Aperia
D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001623:Betamethasone / Q000494:pharmacology*; D005260:Female; D005333:Fetus / Q000187:drug effects / Q000201:enzymology; D005786:Gene Expression Regulation / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D011247:Pregnancy; 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
D012333:RNA, Messenger; D001623:Betamethasone; D000254:Sodium-Potassium-Exchanging ATPase