Developmental and hormonal regulation of SP-A gene expression in baboon fetal lung.
In the present study, we found that surfactant protein A (SP-A) mRNA levels, which are barely detectable in baboon fetal lung at midgestation (92 days), are increased approximately four fold between 125 and 140 days gestation, approximately 7-fold between 140 and 160 days, and approximately 1.5-fold between 160 and 174 days gestation. We also investigated the effects of dibutyryl-adenosine 3',5'-cyclic monophosphate (DB-cAMP) and dexamethasone (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 before culture, were induced after incubation for 5 days in serum-free medium and were markedly stimulated by DBcAMP. Dex caused a dose-dependent inhibition of SP-A mRNA levels and antagonized the stimulatory effect of DBcAMP. 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 DBcAMP. Again, Dex antagonized the induction of SP-A mRNA by DBcAMP. The stimulatory effects of DBcAMP and inhibitory effects of Dex on SP-A mRNA levels in lung tissues of 92- to 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 before 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 DBcAMP and inhibitory effect of Dex on SP-A mRNA levels were relatively modest compared with the effects of these agents on SP-A 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 SP-A gene expression, there is a decrease in responsiveness of the fetal lung to the stimulatory effects of cAMP and inhibitory effects of glucocorticoids on SP-A gene expression.
Department of Pediatrics, University of Texas Health Science Center at San Antonio 78284-7812, USA.
S R
SR
Seidner
M E
ME
Smith
C R
CR
Mendelson
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005865:Gestational Age; D005938:Glucocorticoids / Q000494:pharmacology; D008168:Lung / Q000196:embryology; D008297:Male; D009924:Organ Culture Techniques; D010215:Papio; D011510:Proteolipids / Q000235:genetics*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics
D005938:Glucocorticoids; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D003994:Bucladesine; D003907:Dexamethasone