Heroin induction of lung maturation andgrowth retardation in fetal rabbits

Taeusch, H. William; Carson, Stephen H.; Wang, Nai San; Avery, Mary Ellen

doi:10.1016/s0022-3476(73)80086-1

Cited by 78 publications

(26 citation statements)

References 14 publications

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“…Moreover, the demonstration that both thyroxine [12] and heroin [14] will enhance fetal pulmonary maturation supports the view that the phenomenon occurs via enzyme induction.…”

Section: Introductionsupporting

confidence: 55%

Effects of Steroids on the Enzymatic Pathways of Lecithin Production in Fetal Rabbits

Russell¹,

Nugent²,

Chernick³

1974

Neonatology

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The present study was undertaken to study the effect of corticosteroids on lecithin production in fetal lung. Rabbit fetuses were injected intraperitoneally with hydrocortisone succinate at 24 days of gestation and sacrificed at 27 days. Lung DNA concentration was not changed, but evidence is presented to suggest that total lung DNA content was decreased by saline injection and by steroid injection. Minimum surface tension of pooled lungs was increased by control injections but was reduced to ‘normal’ levels by the steroids. Steroids caused no significant change in lung total phospholipid or lecithin contents. The specific activity of labelled choline, methionine and palmitate indicated increased incorporation of choline and palmitate into lung lecithin in steroid-injected fetuses. It is suggested that steroids accelerate fetal lung development by influencing the composition of surfactant at the alveolar surface.

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“…Moreover, the demonstration that both thyroxine [12] and heroin [14] will enhance fetal pulmonary maturation supports the view that the phenomenon occurs via enzyme induction.…”

Section: Introductionsupporting

confidence: 55%

Effects of Steroids on the Enzymatic Pathways of Lecithin Production in Fetal Rabbits

Russell¹,

Nugent²,

Chernick³

1974

Neonatology

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“…Heroin, however, had no effect on lecithin biosynthesis in the fetal lung cell cultures, although it enhances pulmonary maturation in the fetal rabbit in vivo (22). This suggests that heroin acts on the lung by mechanisms different than those involved in the action of the above hormones.…”

Section: Discussionmentioning

confidence: 86%

“…This surface-active phospholipid is thought t o be produced in alveolar t y p e II cells by two possible pathways (1 1): (1) the incorporation of choline into an a , 0-diglyceride, and (2) the introduction of three methyl groups, derived from methionine, into phosphatidyl ethanolamine. Much interest has been shown in the enhancement of surfactant biosynthesis by pharmacologic means (2) and a number of agents, including corticosteroids (7, 13 -15, 23), thyroxine (20,25), and heroin (22) have been reported t o be active in this respect. We previously described the maintenance in culture of mixed cell populations of fetal rabbit lung in which active incorporation of (' C)palmitate into lecithin was demonstrated and which, in cultures derived from late gestation fetuses, were responsive t o glucocorticoids in terms of increased incorporation of palmitate into lecithin (21).…”

Section: Speculationmentioning

confidence: 99%

Factors Affecting Lecithin Synthesis by Fetal Lung Cells in Culture

Smith

Torday

1974

Pediatr Res

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ExtractIn monolayer cultures prepared from fetal rabbit lungs of 28 days gestation, cortisol, dexamethasone, and L-thyroxine enhanced choline incorporation into lecithin, but had n o effect on the methylation pathway. Heroin did not affect the incorporation of either precursor. Hyperoxia and metabolic acidosis decreased lecithin biosynthesis from both precursors. Over 90% of the lecithin was recovered from the cells after 6 hr of incubation. Release of newly synthesized lecithin was low until 10-1 2 hr, then rapidly increased, reaching 40-50% after 24 hr. The proportion of the lecithin which was disaturated was not different between the intracellular and extracellular compartments. None of the experimental variables altered the degree of saturation. Short term mixed cell cultures provide a useful approach to the study of mammalian lung development. SpeculationThe study of mixed populations of fetal lung cells under conditions of short term monolayer culture provides a simple means of studying the influence of various agents and culture conditions on the biosynthesis of disaturated lecithin, a biochemical index of pulmonary maturation. This approach allows the study of viable, functioning cells under conditions which can be precisely controlled and which can be manipulated in a variety of ways. Inductive effects, which may require a lag time of hours or days, can be demonstrated readily.The maturation of the fetal lung is linked to the formation of a surface-active alveolar lining layer, generally referred t o as the pulmonary surfactant, which contains a high proportion of dipalmityl lecithin (4). This surface-active phospholipid is thought t o be produced in alveolar t y p e II cells by two possible pathways (1 1): (1) the incorporation of choline into an a , 0-diglyceride, and (2) the introduction of three methyl groups, derived from methionine, into phosphatidyl ethanolamine. Much interest has been shown in the enhancement of surfactant biosynthesis by pharmacologic means (2) and a number of agents, including corticosteroids (7, 13 -15, 23), thyroxine (20,25), and heroin (22) have been reported t o be active in this respect. We previously described the maintenance in culture of mixed cell populations of fetal rabbit lung in which active incorporation of (' C)palmitate into lecithin was demonstrated and which, in cultures derived from late gestation fetuses, were responsive t o glucocorticoids in terms of increased incorporation of palmitate into lecithin (21). In the present study, we examine the effects of various agents and culture conditions o n the pathways of lecithin biosynthesis in a similar cell preparation. MATERIALS AND METHODSHam's F-10 tissue culture medium (26) was supplemented with 10% fetal calf serum (27), penicillin (100 U/ml) (28), gentamicin (10 pg/ml) (29), and amphotericin B (5 pg/ml) (30). This preparation will subsequently be referred t o as "control medium." Experimental media were prepared by addition t o the control medium of cortisol (31) at a concentration of 5.5 X 10-6M as describ...

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“…Recent studies in both humans (316) and rabbits (317) have shown that the lungs of female fetuses mature earlier than those of males. Female fetal lungs also respond better to glucocorticoids than those of males at the same gestational age (318)(319)(320) (325) reported that heroin administration to pregnant rabbits accelerated fetal lung maturation. However, heroin had no effect on the rate of choline incorporation into PC in cultured fetal rabbit lung cells (171).…”

Section: Other Factors Which Influence Surfactant Production In the Fmentioning

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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Heroin induction of lung maturation andgrowth retardation in fetal rabbits

Cited by 78 publications

References 14 publications

Effects of Steroids on the Enzymatic Pathways of Lecithin Production in Fetal Rabbits

Effects of Steroids on the Enzymatic Pathways of Lecithin Production in Fetal Rabbits

Factors Affecting Lecithin Synthesis by Fetal Lung Cells in Culture

Lung surfactant.

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