Lung epithelial na channel subunits are differentially regulated
during development and by steroids.
Tchepichev, S., J. Ueda, C. Canessa, B. C. Rossier, and H.
O'brodovich.
MRC Group in Lung Development (Respiratory Research Division of the
Hospital for Sick Children), Department of Paediatrics of the
University of Toronto, Ontario, Canada M5G-1X8, and the Department of
Pharmacology, University of Lausanne, Lausanne, Switzerland
APStracts 2:0193C, 1995.
As 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. Since previous work has shown that the [beta] and [delta]
rENaC subunits of the Na channel are required for maximal
[alpha]rENaC activity, we determined their developmental expression
in the fetal lung. In addition, as thyroid and corticosteroid therapy
can mature the in vivo fetal lamb lung's ability to transport Na, we
wished to determine if such treatment increased the expression of
[alpha], [beta], and [delta]rENaC. Lungs were harvested from normal
rat fetuses of 17 through 22 d of gestation (term = 22 d), normal rat
pups during the first week of life, and adult rats. Initial
expression of [alpha]rENaC was detected at 19 d of gestation and
progressively increased in utero. [beta] and [delta]rENaC mRNA were
not detected until 21 and 22 d of gestation and then only at very low
levels. During the first week after birth the levels of [alpha]rENaC
declined whereas [beta] and [delta]rENaC mRNA levels increased. This
pre and postnatal pattern of [alpha]rENaC expression correlates with
the endogenous glucocorticosteriod levels in the fetus and the rat
pup's early postnatal corticosteroid resistance. Combined or separate
treatment of pregnant rats (16 through 22 d gestational age) with
thyroid releasing hormone (TRH) and / or dexamethasone (DEX) for 48
hours showed that DEX, but not TRH, could increase fetal lung
[alpha]rENaC mRNA levels. In addition, DEX was effective only during
the canalicular stage of fetal lung development. None of these
treatments increased the expression of [beta] or [delta] rENaC
subunits. The DEX effect on [alpha]rENaC in vivo expression occurred
within 8 hours. Neither combined nor separate hormonal therapy
increased [alpha]1 or [beta]1 Na/K ATPase mRNA levels. Neither did
they induce the expression of [alpha]2, [alpha]3, or [beta]2 isoforms
of Na/K ATPase. These results demonstrate that the ontogeny of
[alpha], [beta], and [delta]rENaC is differentially regulated in the
fetal and immediate postnatal lung and that the subunits similarly
show differing responses to exogenous corticosteroids.
Received 28 November 1994; accepted in final form 4 May 1995.
APS Manuscript Number C693-4.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 16 May 1995.