Celsi G, Wang Z M, Akusjärvi G, Aperia A
Department of Pediatrics, St. Göran's Children's Hospital, Stockholm, Sweden.
Pediatr Res. 1993 Jan;33(1):5-9. doi: 10.1203/00006450-199301000-00002.
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.
我们之前报道过,在幼鼠肾皮质中,饱和剂量的糖皮质激素(GC)能迅速增加Na⁺,K⁺-ATP酶mRNA的丰度。我们现在表明这种效应是剂量依赖性的。在10日龄大鼠的肾皮质中,给予2.5微克倍他米松/100克体重时,肾Na⁺,K⁺-ATP酶mRNA会增加。在后续实验中,给予饱和剂量(60微克/100克体重)6小时后进行,我们发现这种效应是年龄依赖性的。在10日龄时对肾皮质α-mRNA的影响最为显著(5.3±0.9倍)。在20日龄大鼠中也发现有显著增加(1.6±0.2倍),但在胎儿和5日龄大鼠中未发现影响。还对肺进行了研究,在围产期观察到最显著的影响(出生前2天为2.0±0.1倍,5日龄时为1.76±0.2倍),但在10日龄和20日龄时对α-mRNA未发现影响。在一个实验方案中,测定了倍他米松对成年去肾上腺大鼠肾Na⁺K⁺-ATP酶mRNA丰度的影响。在这些大鼠中,倍他米松使肾Na⁺,K⁺-ATP酶mRNA显著增加了1.6±0.2倍和1.8±0.3倍。然而,这种效应明显小于在完整的10日龄大鼠中诱导的增加。GC对Na⁺,K⁺-ATP酶mRNA的诱导是年龄和组织依赖性的,并且依赖于GC受体可用性以外的因素。GC敏感期似乎与器官成熟的生理需求相吻合。