TRANSCRIPTIONAL REGULATION OF HUMAN PULMONARY SURFACTANT PROTEINS SP-B AND SP-C BY GLUCOCORTICOIDS

Expression of the pulmonary surfactant-associated proteins SP-B and SP -C is under both developmental and hormonal regulation. We used human fetal lung to investigate developmental changes and the mechanism of g lucocorticoid stimulation of SP-B and SP-C gene expression. There were similar similar to 3-fold increases in SP-B cytoplasmic mRNA content and transcription rate comparing lung samples of 24 wk versus 16 wk ge station. During 5 days of lung explant culture without hormones, the t ranscription rate increased for SP-B and decreased for SP-C, paralleli ng changes in mRNA content. Treatment with 100 nM dexamethasone maxima lly increased transcription of the SP-B gene (similar to 3-fold) and S P-C gene (similar to 11-fold) after 2 and 8 h, respectively, similar t o changes in mRNA content. In dose-response studies, the maximal incre ase in transcription rate occurred at similar to 10 nM dexamethasone f or SP-B and at greater than or equal to 100 nM for SP-C. Induction of SP-B mRNA content and transcription rate were not affected by prior cy cloheximide exposure, whereas induction of SP-C mRNA was decreased by as little as 1 h exposure to inhibitor. We conclude that glucocorticoi ds, acting directly in type II cells, regulate the SP-B and SP-C genes primarily at the level of transcription. Induction of SP-C, but not S P-B, requires ongoing protein synthesis which likely reflects involvem ent of a labile transcription factor. The difference in glucocorticoid sensitivity may indicate that the two surfactant protein genes contai n glucocorticoid response elements with different affinities for recep tor.