Effects of Gestational Age, Dexamethasone, and Metopirone on Lecithin Concentration in Fetal Lung Tissue and Amniotic Fluid in Rats and Guinea Pigs

Nelson, George H.; Eguchi, Katsuto; McPherson, James C.

doi:10.1159/000301395

Cited by 19 publications

(2 citation statements)

References 4 publications

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“…The significant decreases in lung tissue DSPC and DSPCITPL we demonstrated during the final 2 days of gestation, following maternal metyrapone treatment in the rat are in agreement with earlier studies with this agent showing altered surfactant levels or function in rabbits (IS), baboons (12), and guinea pigs (14). Our study, in addition, has demonstrated for the first time a parallel delay following metyrapone in a nonsurfactant-related biochemical system in fetal lung, the antioxidant enzyme system.…”

Section: Discussionsupporting

confidence: 92%

Metyrapone Delays Surfactant and Antioxidant Enzyme Maturation in Developing Rat Lung

1986

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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 me&rapone, an adrenal 11-/3 hydroxylase inhibitor which crosses the ~lacenta and blocks endogenous glucocorticoid synthesis, o; saline. Metyrapone ofispring had significantly decreased lung tissue disaturated phosphatidylcholine and disaturatedphosphatidylcholine/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. (Pediatr Res 20: 672-675, 1986) Abbreviations DSPC, disaturated phosphatidylcholine TPL, total phospholipids AOE, antioxidant enzymes SOD, superoxide dismutase CAT, catalase GP, glutathione peroxidaseThe developmental patterns of the surfactant system and the antioxidant enzyme system of the fetal lung are chronologically similar, with both systems demonstrating marked increases during the final 10-15% of gestation in the several species studied (1-3). Both systems are important in the neonatal adaptation to independent respiration in the relatively oxygen-rich ex utero Received December 16, 1985; accepted March 11, 1986. Address all correspondence to Ilene R. environment. While the surfactant system provides reduction in alveolar surface tension and prevents alveolar collapse at end expiration, the antioxidant enzyme system of the lung prevents cell injury from reactive species of oxygen which are produced under normoxic and hyperoxic conditions (4-6). Multiple lines of evidence indicate that surfactant development is regulated, in part, by endogenous glucocorticoids: elevation of plasma glucocorticoid levels prior to the increase in surfactant (7), the presence of and increase in glucocorticoid receptors in fetal lung prior to elevation in surfactant (8-lo), and delays in surfactant maturation following interference with glucocorticoid production either biochemically (i.e. with metyrapone) or surgically (i.e. by fetal decapitation or hypophysectomy) (1 1-15).It has recently been demonstrated that the maturation of the pulmonary AOE, namely superoxide dismutase, catalase, and glutathione peroxidase, as well as surfactant (as measured ...

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Section: Discussionsupporting

confidence: 92%

Metyrapone Delays Surfactant and Antioxidant Enzyme Maturation in Developing Rat Lung

1986

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“…Metopirone, an inhibitor of cortisol synthesis, has been reported to delay lung maturation in the fetal rabbit (222), rat (164) and guinea pig (164). Glucocorticoids are used clinically in the prevention of RDS in human infants (14,16,170), although there is controversy that such use may have deleterious effects on the development of other organs (223)(224)(225)(226)(227).…”

Section: Glucocorticoidsmentioning

confidence: 99%

Lung surfactant.

Rooney¹

1984

Environ Health Perspect

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Aspects of pulmonary surfactant are reviewed from a biochemical perspective. The major emphasis is on the lipid components of surfactant. Topics reviewed include surfactant composition, cellular and subcellular sites as well as pathways of biosynthesis of phosphatidylcholine, disaturated phosphatidylcholine and phosphatidylglycerol. The surfactant system in the developing fetus and neonate is considered in terms of phospholipid content and composition, rates of precursor incorporation, activities of individual enzymes of phospholipid synthesis and glycogen content and metabolism. The influence of the following hormones and other factors on lung maturation and surfactant production is discussed: glucocorticoids, thyroid hormone, estrogen, prolactin, cyclic AMP, p-adrenergic and cholinergic agonists, prostaglandins and growth factors. The influence of maternal diabetes, fetal sex, stress and labor are also considered. Nonphysiologic and toxic agents which influence surfactant in the fetus, newborn and adult are reviewed.

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Hormonal Influences During Fetal Lung Development

Ballard

1980

Novartis Foundation Symposia

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Effects of Gestational Age, Dexamethasone, and Metopirone on Lecithin Concentration in Fetal Lung Tissue and Amniotic Fluid in Rats and Guinea Pigs

Cited by 19 publications

References 4 publications

Metyrapone Delays Surfactant and Antioxidant Enzyme Maturation in Developing Rat Lung

Metyrapone Delays Surfactant and Antioxidant Enzyme Maturation in Developing Rat Lung

Lung surfactant.

Hormonal Influences During Fetal Lung Development

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