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

Abstract

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...

Identification of LBM180, a Lamellar Body Limiting Membrane Protein of Alveolar Type II Cells, as the ABC Transporter Protein ABCA3

“…In this cell culture system, however, there is a coordinated induction of lamellar body constituents (SP-B, -C, and phospholipids) and ABCA3 of the limiting membrane, further supporting a role for ABCA3 in lamellar body genesis. These findings are in agreement with earlier studies in other systems that have shown temporal correlations between developmental increases in various enzymes involved in synthesis of fatty acids and surfactant proteins (55)(56)(57)(58)(59) and also demonstrated the glucocorticoid-dependent appearance of lamellar bodies and mRNAs of surfactant proteins (60,61). Numerous other studies have also shown surfactant phospholipid (49,50,53,62) and protein (50,51,60,63) production is developmentally regulated during gestation and reaches maximal levels prior to birth.…”

Control of the development of the pulmonary surfactant system in the saltwater crocodile,Crocodylus porosus

“…It is clear that the administered hormones have variable responses at the different stages of incubation, as is also the case in the fetal sheep (22) and rat (47). We speculate that this effect may be the result of the natural variation in maturation rates of different receptors and changes in the rates of PL production throughout incubation.…”

Antenatal Glucocorticoid Corrects Pulmonary Immaturity in Experimentally Induced Congenital Diaphragmatic Hernia in Rats

“…Each trachea was then ligated to maintain the lungs in standardized inflation during fixation. Midcoronal paraffin sections (8 pm) stained with hematoxylin and eosin were studied stercologically with a Nikon Diaphot inverted microscope (Nikon, Garden City, NY) equipped with a 10x objective 526 SUEN ET .4L. with lung maturation (38). Among the C D H rats, the mean lung at the dose of 0.25 mg/kg on d 18.5 and 19.5, only E T l gene glycogen concentrations were significantly decreased by antenatal expression (Fig.…”