Placebo-controlled comparison between a single dose and a multidose of betamethasone in accelerating lung maturation of mice offspring

Stewart, Jeffrey D.; Sieńko, Anna; Gonzalez, Christina L.; Christensen, H.Dix; Rayburn, William F.

doi:10.1016/s0002-9378(98)70140-1

Cited by 49 publications

(23 citation statements)

References 18 publications

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“…The reduced lung weight after exposure to the single dose of BETA was reversed in the young adults, but their effect after repetitive use persisted. These findings are in accord with the study of Stewart et al (14). Willet et al (23) (19) found no long-term differences beyond the immediate perinatal period in the growth and development of BETA-or placeboexposed mouse pups, Okajima et al (25) evaluated the influences of antenatal DEX administration on neonatal lung development in rats.…”

Section: Discussionsupporting

confidence: 81%

A Placebo-Controlled Comparison of Effects of Repetitive Doses of Betamethasone and Dexamethasone on Lung Maturation and Lung, Liver, and Body Weights of Mouse Pups

Ozdemır

2003

Pediatric Research

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The aim of this study was to compare in vivo effects of single and repetitive doses of betamethasone (BETA) and dexamethasone (DEX) administered to pregnant mice on lung maturation and lung, liver, and body weights (LLBW) of their pups. One hundred and eighty gravid Swiss albino mice were randomly assigned to 1 of 6 groups (n ϭ 30) and administered either BETA, DEX, or saline as a single dose at 14 d gestation or repetitive doses twice daily at 14 and 15 d gestation. All the study groups were then divided into three sets (n ϭ 10). The mice in the second sets were redivided into three subsets randomly (including four, three, and three mice). All gestations in the first sets were terminated at 16.5 d gestation to observe the neonatal breathing pattern (scale to 0 -5; 5 is unlabored breathing) of male and female pups whereas other sets had normal delivery. The pups in first, second, and third sets were killed for evaluation in the first set after the evaluation of breathing pattern, in the subsets of second set on postnatal d 1, 3, and 5, and in the third set on postnatal d 90. We recorded maternal body weights at 0 and 16.5 d gestation, and LLBW, the lung/body weight ratio of pups, sex, and the amount of live and dead births per litter. Pups exposed to BETA and DEX had significantly lower maternal weight compared with the saline groups. The death litter size was significantly higher in pups exposed to repetitive doses of DEX than the other treatments. Sex had no significant effect on breathing score and LLBW. Pups exposed to repetitive doses of BETA and DEX presented a higher breathing score than the other groups. The breathing score was significantly higher with BETA than DEX after their repetitive use. The LLBW were significantly less in the treatment groups, especially in the group exposed to repetitive doses of DEX. In conclusion, repetitive doses of BETA and DEX lead to increased fetal lung maturation, but this may be at the expense of fetal and neonatal growth. DEX is less potent in accelerating lung maturation than BETA but it causes more reduction in fetal and neonatal growth. Prenatal GC therapy is routinely used to improve infant outcome after preterm birth, although a number of questions regarding its clinical use could not be answered with available experimental and clinical literature (1). Crowley et al. (2) indicate that prenatal GC therapy is optimally effective if the treatment-to-delivery interval is 24 h to 7 d (3). Many fetuses at risk of preterm delivery do not deliver within 7 d of initial GC treatment. As a result, obstetricians are frequently administering repetitive courses of maternal GC therapy at 7-d intervals to achieve a maximal fetal response in pregnancies with early preterm labor (Ͻ32 wk) (4, 5), although there are no randomized controlled trial data to support this practice.Despite the widespread use of antenatal corticosteroid therapy in obstetric practice, little is known about the effects of synthetic GC on the fetal tissues. Some effects of prenatal GC use on lung structure (...

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Section: Discussionsupporting

confidence: 81%

A Placebo-Controlled Comparison of Effects of Repetitive Doses of Betamethasone and Dexamethasone on Lung Maturation and Lung, Liver, and Body Weights of Mouse Pups

Ozdemır

2003

Pediatric Research

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“…Benefits accelerating lung maturation with glucocorticoid treatment are clear from EW26 and probably diminish somewhat going back to EW22-23 (the lower limit of viability for premature babies) (Ward 1994). Glucocorticoid treatment in mice with comparable lung development (E14-E15·5) accelerates lung maturation; however, stronger treatment on both E14·5 and E15·5 increases lung maturity but also reduces mature lung and lung/body weight ratio; this effect is permanent (Stewart et al 1998), reflecting concerns about glucocorticoid overtreatment prenatally in humans (Lacaze-Masmonteil & Audibert 2000, Seckl et al 2000). There is also ample evidence, from work in the fetal sheep, of glucocorticoid sensitivity in the lung and acceleration of lung maturation by such treatment (Ballard 2000, Forhead et al 2000.…”

Section: Discussionmentioning

confidence: 99%

Ontogeny of glucocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type-1 gene expression identifies potential critical periods of glucocorticoid susceptibility during development

Speirs¹,

Seckl²,

Brown³

2004

Journal of Endocrinology

129

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Glucocorticoids play important roles in organ development and 'fetal programming'. Fetal exposure to excess glucocorticoids reduces birth weight and causes later hypertension. To investigate these processes further we have determined the detailed ontogeny in the mouse of the glucocorticoid receptor (GR) and 11 -hydroxysteroid dehydrogenase type-1 (11 -HSD1), which amplifies glucocorticoid levels locally; the ontogeny was determined using in situ hybridisation from embryonic day 9·5 (E9·5, term=E19) until after birth.At E9·5 fetal GR mRNA levels are very low, except in fetal placenta. GR gene expression rises during gestation with striking tissue-specific differences in timing and extent. Before E13·5, an increase is clear in gastrointestinal (GI) and upper respiratory tracts, discrete central nervous system (CNS) regions, precartilage and especially in the liver (E10·5-E12). Later, further increases occur in lung, GI and upper respiratory tracts, muscle, pituitary and thymus. In a few tissues such increases are temporary, e.g. ureteric ducts (E13·5-E16·5) and pancreas (E14·5-E16·5, expression later falling sharply).Fetal 11 -HSD1 mRNA expression is first clearly observed at E14·5-E15, initially in the fetal placenta then in the umbilical cord. Later, 11 -HSD1 expression is seen as follows: (i) from E15 in lung and liver, rising strongly; (ii) thymus, from E15 (lower level); (iii) at low levels in a few brain regions, including the hippocampus (E16·5+); and (iv) in muscle group fascial planes and tendon insertions.This is the first detailed study of the ontogeny of these two genes and, in combination with previous work on the ontogeny of 11 -HSD2 and the mineralocorticoid receptor, suggests potential critical periods of glucocorticoid sensitivity during development for several organ systems.

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“…Increased oxoreductase (11␤-HSD1) activity at term parallels increased phospholipid biosynthesis (518) consistent with glucocorticoid stimulation of surfactant production (43). Deficiency or inhibition of 11␤-HSD1 reduces fetal lung phospholipid and surfactant synthesis (309,310,649) and increases lung weight (649), the latter consistent with a permanent reduction in lung-to-body weight ratio following prenatal glucocorticoid exposure (667). Thus 11␤-HSD1 inhibition in late pregnancy seems ill-advised.…”

Section: Lungmentioning

confidence: 99%

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

Chapman

Holmes

Seckl

2013

Physiological Reviews

709

601

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Glucocorticoid action on target tissues is determined by the density of “nuclear” receptors and intracellular metabolism by the two isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD) which catalyze interconversion of active cortisol and corticosterone with inert cortisone and 11-dehydrocorticosterone. 11β-HSD type 1, a predominant reductase in most intact cells, catalyzes the regeneration of active glucocorticoids, thus amplifying cellular action. 11β-HSD1 is widely expressed in liver, adipose tissue, muscle, pancreatic islets, adult brain, inflammatory cells, and gonads. 11β-HSD1 is selectively elevated in adipose tissue in obesity where it contributes to metabolic complications. Similarly, 11β-HSD1 is elevated in the ageing brain where it exacerbates glucocorticoid-associated cognitive decline. Deficiency or selective inhibition of 11β-HSD1 improves multiple metabolic syndrome parameters in rodent models and human clinical trials and similarly improves cognitive function with ageing. The efficacy of inhibitors in human therapy remains unclear. 11β-HSD2 is a high-affinity dehydrogenase that inactivates glucocorticoids. In the distal nephron, 11β-HSD2 ensures that only aldosterone is an agonist at mineralocorticoid receptors (MR). 11β-HSD2 inhibition or genetic deficiency causes apparent mineralocorticoid excess and hypertension due to inappropriate glucocorticoid activation of renal MR. The placenta and fetus also highly express 11β-HSD2 which, by inactivating glucocorticoids, prevents premature maturation of fetal tissues and consequent developmental “programming.” The role of 11β-HSD2 as a marker of programming is being explored. The 11β-HSDs thus illuminate the emerging biology of intracrine control, afford important insights into human pathogenesis, and offer new tissue-restricted therapeutic avenues.

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Placebo-controlled comparison between a single dose and a multidose of betamethasone in accelerating lung maturation of mice offspring

Cited by 49 publications

References 18 publications

A Placebo-Controlled Comparison of Effects of Repetitive Doses of Betamethasone and Dexamethasone on Lung Maturation and Lung, Liver, and Body Weights of Mouse Pups

A Placebo-Controlled Comparison of Effects of Repetitive Doses of Betamethasone and Dexamethasone on Lung Maturation and Lung, Liver, and Body Weights of Mouse Pups

Ontogeny of glucocorticoid receptor and 11beta-hydroxysteroid dehydrogenase type-1 gene expression identifies potential critical periods of glucocorticoid susceptibility during development

11β-Hydroxysteroid Dehydrogenases: Intracellular Gate-Keepers of Tissue Glucocorticoid Action

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