SPB gene expression is hormonally regulated by both glucocorticoid and cAMP at the transcriptional level. To characterize the effects of these hormones on SPB protein processing in type 2 cells, we cultured human fetal lung (2123 wk gestation, n = 4) as explants (HFLE) for 1, 3, and 5 d with or without 10 nM Dexamethasone (Dex) or 10 nM Dex/0.1 mM cAMP/0.1 mM IBMX (DCI). After 2h starvation, HFLE were pulsed for 1h with35 Smethionine/cysteinesupplemented media and chased in complete media for 4h. Immunoprecipitation of HFLE homogenates was done using a polyclonal antibody to human SPB. We quantified dpm incorporated into the 42, 2327, and 89 kDa SPB bands, correcting for the numbers of cysteine and methionine in each form. As expected, glucocorticoids ± cAMP increased total dpm incorporated into SPB protein forms over control (3243 ± 593 versus 2236 ± 250 densitometry units, mean±sem, n=24). On days 1, 3, and 5 of culture, control tissue processed 0±0%(mean±sem), 7±5%, and 63±18% of initial incorporated dpm to 8 kDa SPB after 4h, respectively. Hormone treatment markedly enhanced processing to 8 kDa SPB on day 3 (Dex 27±2% and DCI 56±3%) with a less marked effect on day 5 (DCI 81±50%). Processing rates differed considerably between treatments on Day 3. With loss of dpm in 42 and 2327 kD forms (13%/h and 4%/h respectively), there was no accumulation of 8 kD SPB in control samples, consistent with intracellular degradation of these intermediates. After hormone treatment, loss of 42 kD SPB (917%/h) was associated with accumulation of 2327 kD (24%/h) and 8 kD SPB (811%/h). This effect was independent of initial incorporated dpm. We conclude that in addition to transcriptional induction of the SPB gene, hormones have a posttranslational effect on the induction of SPB protein expression. Possible mechanisms include induction of type II cell specific enzymes for further processing of the 2327 kD intermediate and/or increased trafficking of SPB intermediates towards lamellar bodies within the type II cell. Supported by NIH P50HL56401, 5P30HD28815 and the Pennsylvania Thoracic Society.