Evidence for Different Gestation-Dependent Effects of Cortisol on Cultured Fetal Lung Cells

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Abstract
The effect of cortisol (5.5 μM) on primary monolayer cultures of trypsin-dispersed lung cells from rabbit fetuses of 20-28 days gestation was monitored with respect to (a) cellular growth as determined by DNA content after 72 h, at which time all cultures were in the exponential phase of growth, and (b) cellular maturation as reflected by the incorporation of [14C]-palmitate into saturated lecithin and its release into the culture medium. Cortisol significantly increased growth in cultures prepared from 20 day (control: 59.8±8.9 nmol DNA/flask; cortisol: 118.7±15.7, P < 0.001) and 22 day (control: 69.2±17.2; cortisol: 106.7±13.3, P < 0.001) fetuses but had no effect on the growth of cells from 24 or 26 day fetuses. At 28 days, the effect was reversed, cortisol reducing growth by a factor of two (control: 42.0±8.5; cortisol: 19.3±4.0, P < 0.001). Incorporation of palmitate into lecithin was expressed as picomoles incorporated per micromole DNA per flask, thus correcting for differences in the number of cells. Cortisol had no effect on palmitate incorporation until day 26, at which time it caused a slight increase (control: 51.2±5.5: cortisol: 72.8±16.2, P < 0.01) which became very striking by day 28 (control: 19.7±3.1; cortisol; 286.8±47.0, P < 0.001). The proportion of recovered radiolabeled lecithin that was disaturated rose with gestational age from 72% at 20 days to 98% at 28 days. Saturated lecithin made up over 90% at the two gestational ages (26 and 28 days) where cortisol increased palmitate incorporation. In contrast, cortisol had no effect on the incorporation of palmitate into sphingomyelin at any of the gestational ages studied. The results suggest that cortisol may increase fetal pulmonary cellular growth in early gestation while enhancing maturation and slowing growth as term approaches.