Cortisol pretreatment enhances the lung growth response to tracheal obstruction in fetal sheep

We have investigated whether cortisol pretreatment of sheep fetuses will result in a greater liquid accumulation within the lung and a greater lung growth response to obstruction of the fetal trachea. Chronically catheterized fetal sheep received either 1) a cortisol infusion at an increasing dose (1.5-4.0 mg/day) from days 118 to 127 of gestation; the fetal trachea was then obstructed from days 128 to 131 of gestation (n = 4); 2) a saline infusion from days 118 to 127 of gestation; the fetal trachea was then obstructed from days 128 to 131 of gestation (n = 4); or 3) a saline infusion from days 118 to 127 of gestation with no period of tracheal obstruction (control; n = 4). Fetal tracheal pressures were measured from days 128 to 131 of gestation, whereas lung liquid secretion rates and volumes were measured on days 118, 128, and 131 of gestation. On day 131 of gestation, all fetuses were given an intravenous injection of [3H]thymidine and were killed 8 h later. Cortisol pretreatment increased the volume of liquid that accumulated within the fetal lung from 69.5 +/- 4.1 to 96.1 +/- 14.1 ml/kg after 3 days of tracheal obstruction. Similarly, cortisol pretreatment significantly enhanced the increase in lung DNA content from 257.4 +/- 11.0 to 309.1 +/- 16.3 mg/kg after 3 days of tracheal obstruction. We conclude that pretreatment of fetuses with cortisol increases the volume of liquid that accumulates after tracheal obstruction and, as a result, increases the fetal lung growth response to tracheal obstruction.