Metyrapone Delays Surfactant and Antioxidant Enzyme Maturation in Developing Rat Lung

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Abstract
The surfactant system and the antioxidant enzyme system of the fetal lung have chronologically similar developmental patterns and both can be accelerated by the administration of exogenous glucocorticoids. To test whether the antioxidant enzyme system, like the surfactant system, is regulated, at least in part, by endogenous glucocorticoids, we injected pregnant rats for 3 days prior to delivery with metyrapone, an adrenal 11-β hydroxylase inhibitor which crosses the placenta and blocks endogenous glucocorticoid synthesis, or saline. Metyrapone offspring had significantly decreased lung tissue disaturated phosphatidylcholine and disaturated phosphatidylcholine/total phospholipids (p < 0.05) compared to controls at days 21 and 22 of gestation. Activities of the antioxidant enzymes superoxide dismutase, catalase, and glutathione peroxidase were similarly significantly reduced (p < 0.01) in the lungs of metyrapone offspring at both gestational days studied. One day premature metyrapone pups demonstrated poorer survival than control pups from 25 min after delivery (44% survival versus 83%, p < 0.05) to 90 min (6% survival versus 78%, p < 0.01). These findings of delayed maturation of the surfactant and antioxidant enzyme systems following adrenal glucocorticoid blockade suggest that both systems are regulated, at least in part, by an endogenous glucocorticoid mechanism.