REGULATION OF MESSENGER-RNA LEVELS FOR PULMONARY SURFACTANT-ASSOCIATED PROTEINS IN DEVELOPING RABBIT LUNG

Gene transcriptional activities and steady-state mRNA levels have been examined for the surfactant-associated proteins SP-A, SP-B and SP-C i n developing rabbit lung. It was observed SP-C mRNA levels increase ea rly in gestation, while SP-A and SP-B mRNA levels increase rapidly bet ween 26 and 30 days gestation. Transcriptional activities for all thre e surfactant apoproteins increase between 26 and 30 days. Studies cond ucted with fetal lung explants of 26 days gestation demonstrated expos ure to low doses of dexamethasone increases SP-A and SP-C mRNA levels, while high doses stimulate transcription, although this was only sign ificant for SP-C. Time course studies revealed different temporal patt erns and glucocorticoid responses for SP-A and SP-C mRNAs. SP-A. and S P-C mRNA production and steady-state levels were reduced after treatme nt with cycloheximide. In contrast, SP-B gene transcription was select ively stimulated, suggesting involvement of a labile negative regulato ry factory. It is concluded that expression of the three surfactant ap oproteins is independently regulated. Early in gestation, SP-C mRNA le vels may be regulated in vivo through message stabilization. Glucocort icoids can affect SP-A and SP-C mRNA levels in culture at both transcr iptional and post-transcriptional levels. The ability of glucocorticoi ds to influence these processes declines during fetal development.