Accelerated prepartum maturation of the fetal sheep lung with physiological doses of andrenocorticotrophin.

The role of Adrenocorticotrophin (ACTH), administered in physiological doses (12 micrograms/d), on lung maturation was investigated in the intact ovine fetus at 127-130 days of gestation. ACTH1-24 was administered in a pulsatile or continuous dose for 72 hours. Compared to untreated twins (n = 4) and saline infused fetuses (n = 4), the lungs of the pulsatile-ACTH (n = 10) and continuous-ACTH (n = 4) treated fetuses showed accelerated prepartum maturation by all indices used. Lung distensibility (V40-ml of air per g of wet lung at 40 cm H2O pressure), as determined by pressure-volume curves with air was 1.62 +/- 0.18 vs 0.72 +/- 0.23 and 0.66 +/- 0.12 while the stability (Vo-ml of air per g of wet lung at atmospheric pressure) was 0.33 +/- 0.07 vs 0.10 +/- 0.01 and 0.21 +/- 0.09 for the P-ACTH group vs the control groups (P less than 0.005). In the continuous-ACTH group vs their untreated twins the distensibility was 1.58 +/- 0.10 vs 0.56 +/- 0.11 while the stability was 0.83 +/- 0.20 vs 0.09 +/- 0.01 respectively (less than 0.005). Phosphotidylcholine concentration in lavage fluid increased from 0.05 +/- 0.02 mg/g of lung to 0.24 +/- 0.07 in the pulsed-ACTH group compared to untreated twin fetuses (P less than 0.05). Morphologically the lungs of the treated groups were well aerated with thin walled airsacs. In both treated groups, there was a doubling of the adrenal weight (P less than 0.005). Fetal plasma cortisol basal level increased from less than 5 ng/ml to 143.5 +/- 66.5 ng/ml in the continuous-ACTH group while it only rose to 36.6 +/- 7.5 ng/ml in the pulsed-ACTH group by 72 hours. Superimposed on the rise in basal fetal cortisol, there was an acute increase in cortisol temporally related to each ACTH pulse; the peaks reaching levels indistinguishable from the levels of the continuous-ACTH infusion. It is concluded that the administration of low doses of ACTH markedly accelerate prepartum maturation of the intact ovine lung over 72 hours. The mechanism by which ACTH exerts this powerful maturation effect on the fetal lung remains to be elucidated.