SummaryAdrenocortical insufficiency was produced in rat fetuses by surgical decapitation. These animals show low plasma corticosterone levels compared to littermate controls. Lung slices from anencephalic fetuses were found to have reduced incorporation of ['4C]choline into phosphatidylcholine, hence diminished choline pathway activity; this abnormality was present at 21 days of gestation but not at term. Cholinephosphotransferase (CPT), the terminal catalyst of the choline pathway, also showed diminished activity in lungs of anencephalic fetuses, with a mean of 120 pmol/min/mg protein compared to a control value of 190. Dexamethasone treatment of these animals for 6-12 hr led to enhanced choline incorporation rates. Corticosteroid administration also restored CPT activity and even elevated the enzyme to a mean level (340 pmol/min/mg protein) greater than that found in normal fetuses at 21-22 days of gestation. The early pulmonary biochemical effects of dexamethasone in this model were not accompanied by recognizable ultrastructural changes.
SpeculationIt is proposed that glucocorticoids act to influence the timing of l~n~biorhemical development relative to phosphatidylcholin~ svnthesis. Increased amounts of the hormone amear to be suffis e n t but not necessary for this effect since aig'mented choline pathway rates eventually occur in the absence of the corticosteroid stimulus.The low surface tension achieved during expiration by the pulmonary surfactant system is essential for maintenance of alveolar integrity and prevention of the neonatal respiratory distress syndrome (1,8). Synthesis of the major surfactant phospholipid, phosphatidylcholine PC or lecithin (1 ,2-diacyl-sn-glycero-3-phosphorylcholine), is accomplished de novo in fetal lung by incorporation of CDP-choline into 1 ,2-diacylglycerol (7, 9). Investigations by several groups with many species have demonstrated that corticosteroids influence fetal lung development, leading to early increases in the following: ( I ) functional surfactant (19), (2) PC concentration (1 1). (3) PC synthesis per se from choline (6, l l ) , and (4) the apparent number of osmiophilic lamellar bodies in type I1 pneumonocytes (25). Such maturational changes are accompanied by, and are at least partially attributable to, corticosteroid-mediated induction of cholinephosphotransferase or CPT (CDP-cholinc: 1 -2-diglyceride choline phosphotransferase. EC. 2.7.8.2) (1 1).Although adrenocortical insufficiency is rarely encountered in developing fetuses, Jost and Picon (18) have described a model of fetal panhypopituitarism which is produced surgically by decapitating rat fetuses prior to the 18th day of gestation. This experimental model has provided considerable information on the role of adrenocorticoids in regulating liver glycogen metabolism (15) and has been employed by Blackburn and associates (2,3) to investigate fetal lung development. In the latter studies, it has been demonstrated that lungs of anencephalic rat fetuses show: ( I ) morphologic abnormalities characterized b...