DEVELOPMENTAL AND HORMONAL REGULATION OF SURFACTANT PROTEIN A (SP A) GENE
EXPRESSION IN BABOON FETAL LUNG.
Seidner, Steven R., Margaret E. Smith and Carole R. Mendelson.
Department of Pediatrics, University of Texas Health Science Center at San
Antonio,7703 Floyd Curl Drive, San Antonio, Texas 78284-7812, Departments of
Biochemistry and Obstetrics-Gynecology, University of Texas Southwestern
Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, Texas 75235-
9038
APStracts 3:0068L, 1996.
In the present study, we found that SPA mRNA levels, which are barely
detectable in baboon fetal lung at midgestation (92 days), are increased (4-
fold between 125 and 140 days gestation, (5 fold between 140 and 160 days, and
(2-fold between 160 and 174 days gestation. We also investigated the effects
of Bt2cAMP and Dex on SP-A gene expression in lung explants from fetal baboons
at 92, 125, 140, 160 and 174 days of gestation (term=184 days). SP-A mRNA \
levels, which were barely detectable in lung tissues from 92 and 125 day fetal
baboons prior to culture, were induced after incubation for 5 days in serum-
free medium and were markedly stimulated by Bt2cAMP. Dex caused a dose-
dependent inhibition of SP-A mRNA levels and antagonized the stimulatory
effect of Bt2cAMP. SP-A mRNA was detectable in lung tissues from 140 day fetal
baboons before culture; the levels were further induced after culture and were
increased greatly by Bt2cAMP. Again, Dex antagonized the induction of SP-A
mRNA by Bt2cAMP. The stimulatory effects of Bt2cAMP and inhibitory effects of
Dex on SPA mRNA levels in lung tissues of 92-140 day gestational age fetal
baboons were highly similar to those observed in studies using lung explants
of midgestation human abortuses. By contrast, SP-A mRNA was present in
relatively high levels in lung tissues of 160 and 174 day fetal baboons prior
to culture and was relatively unaffected after incubation for 5 days in
control medium. In lung explants from 160 and 174 day fetal baboons, the
stimulatory effect of Bt2cAMP and inhibitory effect of Dex on SPA mRNA levels
were relatively modest as compared to the effects of these agents on SPA mRNA
in fetal lung tissues from 92, 125 and 140 day gestational age fetuses. These
findings suggest that with increased lung maturation and the developmental
induction of SPA gene expression, there is a decrease in responsiveness of the
fetal lung to the stimulatory effects of cyclic AMP and inhibitory effects of
glucocorticoids on SPA gene expression.
Received 11 December 1995; accepted in final form 10 May 1996.
APS Manuscript Number 361-5.
Article publication pending Am. J. Physiol. (Lung Cellular Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 28 May 96