Regulation of Fetal Lung Phosphatidyl Choline Synthesis by Cortisol: Role of Glycogen and Glucose

Gilden, Carl; Sevanian, Alex; Df, Tierney; Sa, Kaplan; Ct, Barrett

doi:10.1203/00006450-197707000-00014

Cited by 63 publications

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“…Nevertheless, hormones that accelerate lung Abbreviations maturation and stimulate surfactant production in the fetus also promote glycogen depletion (1). Glucocorticoids decreased lung T3, triiodothyronine glycogen in vivo in the fetal rabbit (17,18) and mouse (19) while RDS, respiratory distress syndrome dexamethasone and thyroxine had a similar effect in cultured fetal rat lung explants (20). The influence of a combination of these two hormones on this parameter of lung maturation, however, has not previously been reported.…”

mentioning

confidence: 65%

“…Although glucocorticoids (17)(18)(19)(20), thyroid hormone (20), estrogen (44,45), and aminophylline (46,47) have previously been reported to accelerate the normal developmental decrease in lung glycogen, an acceleration of the earlier increase in lung glycogen was reported in only one previous study. Alescio and Dani (48) reported that the glycogen content of 1 1-day fetal mouse lung explants was increased when cultured in the presence of cortisol for 48 h. Effects of hormones on fatty acid synthesis in developing fetal lung have not been extensively examined.…”

Section: Discussionmentioning

confidence: 88%

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Thyroid Hormone Opposes Some Glucocorticoid Effects on Glycogen Content and Lipid Synthesis in Developing Fetal Rat Lung

1986

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ABSTRACT. Because of current interest in use of a com-used prophylactically to accelerate fetal lung maturation and bination of glucocorticoid and thyroid hormones for pre-prevent RDS in human newborns (2, 3) and in at least one vention of respiratory distress syndrome we examined the clinical study (4) thyroxine was also reported to be effective in effects of dexamethasone and triiodothyronine (T3), alone this regard. However, the findings in a recent multicenter study and in combination, on glycogen content and rates of fatty that glucocorticoids are not as efficacious in preventing RDS as acid and phosphatidylcholine synthesis in fetal rat lung. earlier believed and that its effects may be largely confined to The hormones were administered to the mothers on the 2 female infants (5) has led to interest in use of a combination of days before delivery on days 17-22 of gestation. Both glucocorticoids and thyroid hormone for prevention of RDS (6).hormones increased the rate of choline incorporation into Prior to such clinical use, however, it is desirable to have inforphosphatidylcholine, an index of surfactant synthesis, on mation on the interaction of these hormones in the acceleration day 20 just prior to the normal developmental surge but of lung maturation in animals. had no effect on this parameter on days 19, 21, or 22.Previous studies in animals have shown that a combination of There is a developmental increase in lung glycogen on days glucocorticoid and thyroid hormones is more effective than either 17-20 with a decrease thereafter and a developmental hormone alone in accelerating fetal lung maturation and stimuincrease in the rate of fatty acid synthesis between days 20 lating surfactant production. In a morphological study in the and 21. The increases in glycogen content and fatty acid fetal rat, Hitchcock (7) reported maximal acceleration of lung synthesis were accelerated by dexamethasone and pre-maturation when glucocorticoids and thyroxine were both presvented by T3 and when the hormones were administered ent. Similarly, a synergistic interaction between glucocorticoids together T3 antagonized the stimulatory effects of dexa-and thyroid hormone in stimulating synthesis of phosphatidylmethasone on these parameters. Both dexamethasone and choline and disaturated phosphatidylcholine, the major compo-T3 accelerated the normal developmental decrease in lung nent of pulmonary surfactant (I), was demonstrated in fetal rat glycogen later in gestation and the effects of the two lung in vivo (8,9) and in fetal rat (10, 1 I), rabbit (12), and hormones on this parameter were additive. The combina-human (1 3) lung in culture. tion of dexamethasone and T3 led to significantly smaller In addition to morphology and synthesis of surfactant phosfetuses and increased mortality late in gestation. These pholipids, lung maturation may also be assessed by other criteria. data show that glucocorticoid and thyroid hormones have An increase followed by a decrease in glycogen content is a opposite as well as common effects on...

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mentioning

confidence: 65%

Section: Discussionmentioning

confidence: 88%

Thyroid Hormone Opposes Some Glucocorticoid Effects on Glycogen Content and Lipid Synthesis in Developing Fetal Rat Lung

1986

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“…It has been reported elsewhere (12) that in fetal rat lung explants 17P-estradiol decreased lung glycogen although the effect was much less marked than in the present study. Glucocorticoids also decrease lung glycogen both in fetal rabbits in vivo (8,34) and in Table 3.…”

Section: Resultsmentioning

confidence: 99%

“…In comparing results from investigations conducted by this laboratory and others on lung maturation, a number of noteworthy similarities were found between the effects of estrogen and glucocorticoids. Both accelerate morphologic maturation of the fetal lung (18) and deplete its glycogen content (8,34). Both increase the amount of phosphatidylcholine as well as the phosphatidylcho1ine:sphingomyelin ratio in lung lavage and increase the rate of choline incorporation into phosphatidylcholine in lung slices (33).…”

Section: Effect Of I7p-estradiol On Fetal Rabbit Lung and Liver Glycomentioning

confidence: 99%

Effects of Estrogen on Fetal Rabbit Lung Maturation: Morphological and Biochemical Studies

et al. 1981

Pediatr Res

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Summary17P-Estradiol (0.44 to 4.4 &kg) was intramuscularly administered to pregnant rabbits on day 25 or 26 of gestation, and the fetuses were delivered by cesarean section 24 hr later. On light microscopy, the lungs from the treated group had larger alveoli and thinner interalveolar septa than did those from the controls at the same gestational age. The 1umen:septa ratio was 0.62 + 0.06 in the control group and 0.88 + 0.05 in the treated group ( P < 0.01). Blood vessels in the lungs of the treated group were also more mature than were those in the control group. Alveolar epithelial cells consisted of 52% undifferentiated, 21% type 11, and 27% type I cells in the control group. In the estrogen-treated group, the corresponding distribution was 25, 29, and 45%. There were 0.82 -+ 0.16 lamellar bodies per alveolar cell in the treated group compared to 0.38 k 0.06 in the controls (P < 0.05). Estrogen decreased fetal lung glycogen content from 247 + 15 pg/mg protein to 70 9 on day 26 and from 103 -+ 13 to 13 + 2 on day 27 ( P < 0.001). Estrogen administration increased the rate of incdrporation of choliie into phosphatidylcholine in fetal lung slices. decreased the rate of thymidine incorporation into DNA, but had no effect on the rates bf incorporatibn of ethanolamine into phosphatidylethanolamine or of leucine into protein. These data indicate that estrogen accelerates the rate of fetal lung maturation. It appears to stimulate lung differentiation at the expense of lung growth. SpeculationEstrogen may be involved in the physiologic control of fetal lung maturation and pulmonary surfactant production.We have previously shown that administration of 17/3-estradiol to pregnant rabbits at 25 to 26 days gestation (term is 31 days) accelerates fetal lung maturation and stimulates production of pulmonary surfactant (16,17). Thus, maternal estrogen administration has the following effects on the fetal lung: it increases the amount of total phospholipid and phosphatidylcholine as well as the phosphatidylcholine:sphingomyelin ratio in lung lavage (17), it increases the rate of choline incorporation into phosphatidylcholine in lung slices (16), and it increases the activities of pulmonary cholinephosphate cytidylyltransferase and lysolecithin acyltransferase (16), enzymes involved in the synthesis of total and disaturated phosphatidylcholine, respectively (33). Gross et al. (12) reported that estrogen accelerates maturation of fetal rat lung in organ culture. This fmding suggests that estrogen has a direct effect on the fetal lung.The purpose of the present study was to further characterize the effects of estrogen on fetal lung maturation. Inasmuch as there are distinct morphological changes during maturation of the fetal lung (2), we examined the effects of estrogen on these parameters of lung maturation. In addition, we determined the effect of estrogen on lung glycogen content because this decreases toward the end of gestation in a number of species (4,23,36), and it has been postulated that glycogen may provide substrate o...

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“…44). fhese maturational processes-the ialI & pu&onary glycogen; the rise in surfactant svnthesis, and the amearance of lamellar bodies-are all accelerated by the admini'siration of exogenous glucocorticoids (14,23,29,31,32). In a retrospective analysis, Robert et al (3 1 ) showed that infants of diabetic pregnancies have a 5.6 times greater risk of developing the respiratory distress syndrome than those of nondiabetic gestations.…”

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Delay in Pulmonary Glycogen Degradation in Fetuses of Streptozotocin Diabetic Rats

et al. 1982

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SummaryThe developmental profile of pulmonary glycogen was investigated in fetuses of rats made diabetic before conception with the injection of 40 mg/kg streptozotocin.Lungs of control litters showed increasing pulmonary glycogen concentration from day 16-20, followed by significant decline by term (= 22 days). In contrast, the diabetic litters, which had pulmonary glycogen concentration equal to controls until day 20, showed significantly higher glycogen values ( P < 0.01) on days 21and 22, consistent with a delay in glycogen degradation. This coincided with the fiding of decreased amounts of fetal pulmonary phosphatidylcholine and disaturated phosphatidylcholine on day 21 of the diabetic gestation (P < 0.05), but not before that time.Pulmonary glycogen phosphorylase A activity was significantly decreased in the diabetic litters on the final days of gestation, at the same time that the delay in glycogen breakdown became evident. Pulmonary glycogen synthase activity did not differ in the control and diabetic fetuses. SpeculationThe delay in pulmonary glycogen degradation seen in the fetus of the diabetic gestation is thus temporally related to the delay in lung maturation seen in this model and may be secondary to a decrease in the activity of the glycogenolytic enzyme phosphorylase A. Decreased availability of pulmonary glycogen stores for surfactant synthesis may be important in elucidating the mechanism of the delayed pulmonic maturation seen in fetuses of diabetic pregnancies.There is a growing body of evidence that implicates glucose, and its storage form glycogen, in the biosynthesis of surface active phospholipids in the developing fetus (11,36,42). Pulmonary glycogen content, which increases throughout most of gestation, falls rapidly near term, coincident with the appearance of lamellar bodies in alveolar type I1 cells and with an increase in choline incorporation into the surface active ~h o s~h o l i~i d fraction (27. 44). fhese maturational processes-the ialI & pu&onary glycogen; the rise in surfactant svnthesis, and the amearance of lamellar bodies-are all accelerated by the admini'siration of exogenous glucocorticoids (14,23,29,31,32). In a retrospective analysis, Robert et al. (3 1 ) showed that infants of diabetic pregnancies have a 5.6 times greater risk of developing the respiratory distress syndrome than those of nondiabetic gestations. It might therefore be expected that fetuses of diabetic pregnancies would have coincident aberrations in surfactant production and pulmonary glycogen metabolism. Indeed, increased pulmonary glycogen stores have been observed in fetal (39) and newborn (35) animals born to diabetic mothers; however, others report diminished glycogen content in the lungs of fetuses of experimental diabetic pregnancies (43).We used the streptozotocin diabetic rat as a means of studying fetal pulmonary glycogen metabolism throughout the diabetic gestation, in an effort to clarify the role of substrate availability with respect to the observed delay in lung maturation seen in the di...

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Regulation of Fetal Lung Phosphatidyl Choline Synthesis by Cortisol: Role of Glycogen and Glucose

Cited by 63 publications

References 0 publications

Thyroid Hormone Opposes Some Glucocorticoid Effects on Glycogen Content and Lipid Synthesis in Developing Fetal Rat Lung

Thyroid Hormone Opposes Some Glucocorticoid Effects on Glycogen Content and Lipid Synthesis in Developing Fetal Rat Lung

Effects of Estrogen on Fetal Rabbit Lung Maturation: Morphological and Biochemical Studies

Delay in Pulmonary Glycogen Degradation in Fetuses of Streptozotocin Diabetic Rats

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