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

Russell, Brian; Nugent, Lynn; Chernick, Víctor

doi:10.1159/000240662

Cited by 35 publications

(12 citation statements)

References 7 publications

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“…These results confirm others' observations (3,18,22,25) and indicate that the dose and timing of the maternally administered hydrocortisone in this experiment was sufficient to cause some effect on the fetuses. The reduction of glucocorticoid-treated fetal lung weight probably resulted from a decrease of the water content (3) or an inhibition of cell proliferation (3,14).…”

Section: Resultssupporting

confidence: 92%

“…However, this was not apparent in this study (Table 2), nor has it been consistently observed by others (1, 10,12,25). These different observations could result from diverse techniques of lung PC measurement based on either dry lung (8,23) or wet lung (this study, 1, 10,12,25).…”

Section: Resultscontrasting

confidence: 56%

“…In contrast to the discrepant results of the effect of steroids on specific enzyme induction in fetal lung, glucocorticoids have always stimulated the general incorporation of choliie or other substrates into fetal lung PC in vivo (I), in tissue slices (2,8,22,25), and in tissue culture (6,26). In addition to specific enzyme induction, glucocorticoids might affect substrate uptake by the intact cells, not just choline, but also other substances, such as the incorporation of glucose into glycogen and PC (lo), palmitate into PC (25), and ethanolamine into phosphatidylethanolamine (22).…”

Section: Resultsmentioning

confidence: 99%

“…In addition to specific enzyme induction, glucocorticoids might affect substrate uptake by the intact cells, not just choline, but also other substances, such as the incorporation of glucose into glycogen and PC (lo), palmitate into PC (25), and ethanolamine into phosphatidylethanolamine (22).…”

Section: Resultsmentioning

confidence: 99%

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Effect of Hydrocortisone on the Metabolism of Phosphatidylcholine in Maternal and Fetal Rabbit Lungs and Livers

1979

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SummaryIt has been observed that glucocorticoids stimulate fetal lung maturation. This study examined the effects of glucocorticoids on the phosphatidylcholine (PC) metabolism in maternal and fetal lungs and livers. At 24 days of gestation, pregnant does were injected im with either hydrocortisone or an equal volume of saline. At 27 days of gestation, the maternal and fetal lungs and livers were removed for study. Maternal hydrocortisone treatment significantly decreased the fetal body weight and lung weight, but had no effect on the weights of fetal liver or the ratios of maternal lung/body or liver/body weights. Concentrations of protein, total phospholipids, or PC of fetal lung and liver and of maternal liver were not affected by hydrocortisone. However, the amounts of maternal lung protein, total phospholipids, and PC were significantly increased. No stimulation by hydrocortisone was seen in the specific activities of the enzymes: choline kinase, phosphocholine cytidyltransferase, and choline phosphotransferase of cytidiie 5'-diphosphocholine (CDPcholine) pathway and IysoPC-IysoPC acyltransferase, lysophosphdipase, and acyl-CoA IysoPC acyltransferase of PC-IssoPC cycle pathway.Maternal administration-of hydrocohisone stimulated the incorporation of [methyl-14CI choline into fetal lung PC. Additionally, hydrocortisone also accelerated the secretion of PC from maternal lung tissue. The acceleration of the secretion of PC was not observed in the fetal lung tissue, possibly because of a low basal secretory rate. The acceleration of PC secretion by hydrocortisone in maternal lung may suggest a relation of this mechanism to the fetal lung maturation affected by steroids. SpeculationOne biochemical effect of antenatal maternal hydrocortisone is the acceleration of choline incorporation into fetal lung PC. Maternally administered glucocorticoids, in addition to affecting fetal lung, might also affect maternal lung and liver PC metabolism by alteration of enzyme activity or changing turnover or transfer rates. Though studied indirectly, hydrocortisone might stimulate the secretion of lung PC onto the alveolar surface.Lung surfactant is normally layered at the air-water interface of alveoli and stabilizes alveolar deflation during respiration., Phosphatidylcholine (1,2-diacyl-sn-glycero-3-phosphocholine) is the major lung surface-active component (9, 29). Insufficiency of this phospholipid in lungs of neonates is generally related to the respiratory distress syndrome (RDS) (7).A number of studies have demonstrated that maternally administered glucocorticoids in humans can decrease RDS (1 1, 17) and density of air space (12, 13). Lung PC is mainly synthesized by the CDP-choline pathway, and possibly remodeled by the deacylation-reacylation and deacylation-transacylation pathways (PCIysoPC cycle pathway) to form the highly disaturated PC (9, 29). Several studies have suggested that the acceleration of fetal lung surfactant by prenatal administration of glucocorticoids is related to the induction of the enzymes of these ...

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Section: Resultssupporting

confidence: 92%

Section: Resultscontrasting

confidence: 56%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Effect of Hydrocortisone on the Metabolism of Phosphatidylcholine in Maternal and Fetal Rabbit Lungs and Livers

1979

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“…We have found previously that saline injection was associated with changes in lung enzyme systems in the fetal rabbit (15). It is suggested that either the stress of the operative procedure or the injection per se could cause an increased production of endogenous cortisone, thereby affecting CA activity; this supports the notion that we studied a physiologic rather than a pharmacologic effect of steroid.…”

Section: Discussionsupporting

confidence: 85%

Enhanced Fetal Erythrocyte Carbonic Anhydrase Activity by Hydrocortisone

1976

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Pediat. Res. 10: 779-782 (1976) Carbonic anhydrase hyaline m e m b r a n e disease ExtractThe present experiments were undertaken to study the effect of exogenous corticosteroids on carbonic anhydrase ( C A ) activity in fetal erythrocytes. Rabbit fetuses from 24 days of gestation to term (31 days) were injected intraperitoneally with either 0.2 ml of 0.9% saline or 2.5 mg hydrocortisone succinate. Nonoperated, noninjected animals served as controls. Carbonic anhydrase activity measured at 24 hr after injection was increased in the saline-injected group at all ages studied when compared with the noninjected fetuses. A marked increase (2-to 7-fold) in enzyme activity was demonstrated after steroid injection at 24 but not 48 hr after treatment. An increase in CA activity was also demonstrated after incubating fetal erythrocytes for 2, 4, and 8 hr in the presence of hydrocortisone succinate. It is suggested that low CA activity in infants with hyaline membrane disease ( H M D ) may reflect lack of enhancement by steroid. SpeculationGlucocorticoids are probably important in the enhancement of the development of numerous organ systems, including lung, gut, and blood, in preparation for extrauterine life. Low CA activity in the cord blood of infants with H M D may reflect a lack of steroid activation of a number of fetal enzyme systems, including those necessary for surfactant synthesis.Carbonic anhydrase is an enzyme that reversibly catalyzes the hydration of carbon dioxide to bicarbonate and hydrogen ions. Early investigations have determined that CA activity is lower in the fetus than in the newborn and that both have values lower than the adult (I, 3, 6, 18). More recently, investigators from the United States have demonstrated that the CA activity in the cord blood of infants with HMD is markedly lower than in infants of the same gestational age without HMD (7,8,16), although the reason for this remains unknown. However, Logan et a/. (10) studied infants with and without HMD and measured CA activity in erythrocytes obtained within the first 24 hr of birth. They found no difference in CA activity. Several investigators have shown an acceleration of fetal lung maturation by the in vivo administration of corticosteroids (4, 5, 9, l I, 15, 20). With this in mind, the present study was undertaken to determine whether steroids could also enhance carbonic anhydrase activity in the fetus, and whether this might explain the discrepant results reported for CA activity in infants with HMD. M E T H O D SForty-two pregnant New Zealand albino rabbits from 24 to 30 days of gestation were used for this study. The does were mated with two bucks within a 2-hour period and this time was considered to be day 0 of gestation. The rabbits were then removed and kept in separate cages for the duration of the experiment. On the appropriate day, a laparotomy was performed on the adults through a.midline incision. The fetal abdomen was identified by palpation and an injection of either 0.2 ml 0.9% saline or 2.5 mg hydrocortisone succina...

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Hormones and the lung. I. Thyroid hormones and glucocorticoids in lung development

Hitchcock

1979

Anat. Rec.

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It has been proposed that thyroid hormones may have a role in the regulation of lung development and the maturation of the surfactant system. The purpose of this study was to examine the effects of exogenous thyroxine (T,) on rat lung development and to investigate possible interactions of this hormone with the glucocorticoids, other hormones implicated in the regulation of lung development.A number of different experimental protocols were utilized: T, was administered to day 17 and 18 rat fetuses from untreated animals as well as from animals which had been adrenalectomized or treated with the 11-P-hydroxylase inhibitor, Metopirone; replacement hydrocortisone was administered to some groups. Sham-operated and untreated animals were included as controls. Animals were sacrificed from days 19-22 (term, day 22-23) of gestation and the fetal lungs were examined. Accelerated lung development was observed in all experimental groups receiving T,. Alveolar epithelial cells were more differentiated in comparison to controls. Glycogen deposits were diminished, cell flattening was more advanced, mitochondria, Golgi complexes and rough endoplasmic reticulum were more prominent, and lamellar bodies, storage sites for pulmonary surfactant, were greatly increased in number. Secretion of lamellar bodies into the alveolar space was also stimulated. The results also indicated that T, and glucocorticoids act together in the acceleration of lung development. Under conditions of decreased glucocorticoids (Metopirone treatment and adrenalectomy), stimulatory effects of T, were still evident but less pronounced; hydrocortisone replacement increased the observed stimulation. Maximal acceleration of lung development was observed subsequent to T, and uncontrolled surgical stress. These results demonstrate that T, can accelerate rat lung development and that this acceleration is maximal in the presence of glucocorticoids.It is now well established that immaturity of the lung, leading to deficient pulmonary surfactant stores a t birth, is one of the major etiologic factors leading to the respiratory distress syndrome (RDS) of the newborn (for reviews, see Comroe, '77; Farrell and Avery, '75; Gluck, '72; King, '74; Scarpelli, '68; Tierney, '74). This finding has led to many investigations concerning the factors which may control the maturation of the lung as well as the initiation and regulation of the synthesis of '76) and its subsequent release onto the alveolar surface.Since the possibility that adrenal glucocorticoids might influence lung maturation was initially suggested (Buckingham et al., '68) and subsequently supported in studies by Liggins ('691, a large body of morphologic, biochemical and physiologic data has accumulated indicating that glucocorticoids can ac- celerate lung development and the maturation of the surfactant system (for reviews, see Avery, '75; Ballard and Ballard, '76; Ballard et al., '77; Farrell, '77). Though less well established as a regulatory factor, a number of experimental studies have indicate...

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

Cited by 35 publications

References 7 publications

Effect of Hydrocortisone on the Metabolism of Phosphatidylcholine in Maternal and Fetal Rabbit Lungs and Livers

Effect of Hydrocortisone on the Metabolism of Phosphatidylcholine in Maternal and Fetal Rabbit Lungs and Livers

Enhanced Fetal Erythrocyte Carbonic Anhydrase Activity by Hydrocortisone

Hormones and the lung. I. Thyroid hormones and glucocorticoids in lung development

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