Pulmonary maturation in the hypophysectomised ovine fetus. Differential responses to adrenocorticotrophin and cortisol.

Pulmonary maturation in six ovine fetuses hypophysectomised by a cryosurgical method at 0.7-0.8 of pregnancy and delivered by hysterotomy at 152.2 +/- 2.9 (SD) days was compared with that in seven control fetuses delivered at 144.5 +/- 3.5 days. Both the wet and the dry weight of the lungs was less in the hypophysectomised fetuses but total DNA did not differ. Lung volumes at 40 cm of H2O and at 5 cm of H2O on deflation in hypophysectomised fetuses were less than one-third that of controls. Saturated phosphatidylcholine, as an estimate of surfactant, was lower in both lung tissue and lavage fluid. A further group of hypophysectomised fetuses was infused intravenously either with cortisol at 1 mg/h for 72 h (n = 6), or with ACTH1-24 at 5 microgram/h for 84 h (n = 6) before delivery at 155.0 +/- 2.1 days and 154.2 +/- 3.9 days respectively. None of the indices of pulmonary maturation in the cortisol-treated fetuses differed from those in untreated hypophysectomised fetuses whereas values for lung volumes at 40 and 5 cm of H2O in ACTH-treated fetuses were more than twice those of untreated hypophysectomised fetuses and did not differ significantly from controls. In addition, the amount of saturated phosphatidylcholine in lavage fluid was greater in ACTH-treated fetuses (0.13 +/- 0.10 mg/g) than in untreated hypophysectomised fetuses (0.04 +/- 0.48 mg/g). Lung volume at 40 cm of H2O in four fetuses that were thyroidectomised at the time of hypophysectomy responded to ACTH as in hypophysectomised fetuses with intact thyroids but other indices were unaffected. We conclude that hypophysectomy retards pulmonary maturation in fetal sheep. Since ACTH restores distensibility and increases alveolar surfactant in the absence of other pituitary hormones it is likely that ACTH has a major role in lung maturation. The lack of response to cortisol suggests that the effect of ACTH is not mediated only by circulating cortisol.