SENSITIVE PERIODS FOR GLUCOCORTICOIDS REGULATION OF NA+,K+-ATPASE MESSENGER-RNA 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 mug betamethasone/100 g body weight. In subsequent experiments, performed 6 h after a saturating dose (60 mug/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.