Lung epithelial Na channel subunits are differentially regulated during development and by steroids.
Because the alpha-subunit of the rat lung epithelial Na channel (rENaC) is not expressed until late fetal gestation, the developmental immaturity of alpha-rENaC may be involved in the premature fetal lung's inability to mount a Na-absorptive response to appropriate agonists. As previous work has shown that the beta- and gamma-rENaC subunits of the Na channel are required for maximal alpha-rENaC activity, we determined their developmental expression in the fetal lung. In addition, because thyroid and corticosteroid therapy can mature the in vivo fetal lamb lung's ability to transport Na, we wished to determine whether such treatment increased the expression of alpha-, beta-, and gamma-rENaC. Lungs were harvested from normal rat fetuses of 17 through 22 days gestation (term = 22 days), normal rat pups during the first week of life, and adult rats. Initial expression of alpha-rENaC was detected at 19 days gestation and progressively increased in utero. beta- and gamma-rENaC mRNA were not detected until 21 and 22 days gestation, and then only at very low levels. During the first week after birth, the levels of alpha-rENaC declined, whereas beta- and gamma-rENaC mRNA levels increased. This pre- and postnatal pattern of alpha-rENaC expression correlates with the endogenous glucocorticosteroid levels in the fetus and the rat pup's early postnatal corticosteroid resistance. Combined or separate treatment of pregnant rats (16 through 22 days gestational age) with thyroid-releasing hormone (TRH) and/or dexamethasone (Dex) for 48 h showed that Dex, but not TRH, could increase fetal lung alpha-rENaC mRNA levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Tchepichev
S
S
Hospital for Sick Children, Department of Paediatrics, University of Toronto, Ontario, Canada.
Ueda
J
J
Canessa
C
C
Rossier
B C
BC
O'Brodovich
H
H
D000305:Adrenal Cortex Hormones / Q000494:pharmacology*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D003907:Dexamethasone / Q000494:pharmacology; D005314:Embryonic and Fetal Development; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D005333:Fetus / Q000378:metabolism* / Q000502:physiology; D008168:Lung / Q000196:embryology* / Q000378:metabolism*; D051381:Rats; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
D000305:Adrenal Cortex Hormones; D015222:Sodium Channels; D013973:Thyrotropin-Releasing Hormone; D003907:Dexamethasone; D000254:Sodium-Potassium-Exchanging ATPase