Sensitive Periods for Glucocorticoids' Regulation of Na⁺,K⁺-ATPase mRNA in the Developing Lung and Kidney

Abstract

ABSTRACT: 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 μg beta-methasone/100 g body weight. In subsequent experiments, performed 6 h after a saturating dose (60 μg/100 g body weight), we show that the effect is age dependent. The most marked effects on renal cortical α-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 α-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.