Glucocorticoids are often applied in neonatology and perinatology to fight the problems of respiratory distress and chronic lung disease. There are, however, many controversies regarding the adverse side effects and long-term clinical benefits of this therapeutic approach. In rats, glucocorticoids are known to seriously impair the formation of alveoli when applied during the first two postnatal weeks even at very low dosage. The current study investigates short-term and long-term glucocorticoid effects on the rat lung by means of morphologic and morphometric observations at light and electron microscopic levels. Application of a high-dosage protocol for only few days resulted in a marked acceleration of lung development with a precocious microvascular maturation resulting in single capillary network septa in the first 4 postnatal days. By postnatal d 10, the lung morphologic phenotype showed a step back in the maturational state, with an increased number of septa with double capillary layer, followed by an exceptional second round of the alveolarization process. As a result of this process, there was an almost complete recovery in the parenchymal lung structure by postnatal d 36, and by d 60, there were virtually no qualitative or quantitative differences between experimental and control rats. These findings indicate that both dosage and duration of glucocorticoid therapy in the early postnatal period are very critical with respect to lung development and maturation and that a careful therapeutic strategy can minimize late sequelae of treatment. GC therapy is widely used in the prenatal and postnatal periods either as a prophylactic or curative measure. Use of prenatal GCs is often motivated by the observed positive effects on lung maturation and surfactant production in preterm babies (1, 2), who otherwise stand a high chance of developing respiratory distress syndrome (3) and subsequent chronic lung disease, also known as bronchopulmonary dysplasia (4, 5). The positive effects of postnatal GCs on pulmonary inflammatory processes (6, 7) and the prophylactic effects against hyperoxic lung injury (8) seem to improve the survival chances of preterm neonates. In perinatal medicine, a variety of therapeutic schemes have been adopted, but controversies regarding the long-term benefits and the negative side effects of GC in neonatology abound (9 -11). Indeed, besides the apparent benefits of GC therapy, adverse effects on lung maturation have been reported in animal experiments (12, 13). Furthermore, reserves have been expressed over the general outcome of treated newborns (14,15). In the recent past, there have been numerous studies on the positive and negative effects of postnatal GC therapy, but as noted by Barrington (16), there are no published long-term pulmonary data.Previously we have indicated that long-term administration of minute doses of GC results in a permanent impairment of lung alveolarization in postnatal rats (17,18). Alveolarization is achieved by subdivision of the preexisting saccular air spaces ...
