Prenatal dexamethasone administration disrupts the pattern of cellular development in rat lung

Navarro, Hernán A.; Kudlacz, Elizabeth M.; Eylers, J.P.; Slotkin, Theodore A.

doi:10.1002/tera.1420400504

Cited by 30 publications

(13 citation statements)

References 10 publications

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“…In keeping with earlier reports [6,31], dexamethasone administration slowed mater nal weight gain but did not reduce the propor tions of dams delivering pups or litter size at birth (data not shown). However, prenatal dexamethasone treatment caused a signifi cant inhibition of postnatal body and brain region growth ( fig.…”

Section: Resultssupporting

confidence: 92%

Glucocorticoids and the Development of Neuronal Function: Effects of Prenatal Dexamethasone Exposure on Central Noradrenergic Activity

et al. 1992

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Although glucocorticoids slow the development of most cell types, they have been hypothesized to promote the differentiation of catecholaminergic cells. In the current study, pregnant rats were given dexamethasone on gestational days 17, 18 and 19, and the functional state of noradrenergic synaptic activity was assessed throughout postnatal development by measurements of transmitter levels and turnover, and receptor binding capabilities. Despite growth inhibition caused by dexamethasone, the steroid treatment had little or no effect on transmitter levels or receptor binding and accelerated the maturation of norepinephrine turnover in a regionally selective manner. Effects were most notable in the midbrain and brainstem, where turnover rose to maximum levels 1–2 weeks in advance of controls. Turnover also leveled off prematurely in the dexamethasone group, leading to deficits in the postweaning period and into young adulthood. Although similar patterns were obtained in other, later-developing regions, the effects were less consistent and robust; the smaller effects also extended to dopamine turnover. These results suggest that glucocorticoids have a specific promotional effect on the development of central catecholaminergic activity and that administration of exogenous steroids during critical periods of development can lead to lasting functional abnormalities.

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Section: Resultssupporting

confidence: 92%

Glucocorticoids and the Development of Neuronal Function: Effects of Prenatal Dexamethasone Exposure on Central Noradrenergic Activity

et al. 1992

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“…This contrasts with the findings of Ellington et al [35] and Fussel and Kelly [36] who both described a glucocorti coid-induced suppression of body and lung growth, the former in ferrets during weeks [8][9][10][11][12][13][14][15][16][17][18][19], the latter in rats with a body weight of 100 g. This indicates that species and/or tim ing of treatment may greatly influence the response.…”

mentioning

confidence: 71%

Influence of Postnatally Administered Glucocorticoids on Rat Lung Growth

Tschanz¹,

Damke²,

Burri³

1995

Neonatology

175

104

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Postnatal formation of alveoli can be largely prevented by glucocorticoid treatment, which accelerates alveolar wall thinning and inhibits outgrowth of new interalveolar septa. Since a double capillary network is a prerequisite for interalveolar wall formation, we hypothesized that glucocorticoid treatment inhibited alveolar formation, indirectly, by inducing precocious microvascular maturation. Between 4 and 60 days we followed up qualitatively and quantitatively the effects of 2 weeks (days 2–15) of daily Decadron® (Dexamethasone phosphate) injections on the lung structure. Glucocorticoid induced only small changes in body weight or lung volume. However, during the first 2 weeks, it accelerated alveolar wall thinning and microvascular maturation and partly suppressed the outgrowth of new interalveolar septa. In Decadron-treated rats, the interstitial tissue mass was significantly reduced during the first 2 weeks, and a larger alveolar surface area was endowed with a capillary monolayer on days 10 and 13. One week after drug withdrawal, the trend towards precocious maturation of the lung was reversed. Lipofibroblasts reappeared, and inter-airspace septa regressed towards a more immature state. We found indications of a second burst of alveolization by resumption of secondary septa formation. The late sequelae of Decadron treatment (day 60) were manifested as an ‘emphysematous’ condition of the lungs, with larger and fewer airspaces, the delayed alveolization being insufficient to compensate for the initial deficit.

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“…Treatment of rats throughout pregnancy with a modest dose of dexamethasone (a synthetic glucocorti coid which crosses the placenta), reduces average birth weight and produces elevated blood pressures in the adult offspring, many months after the last exposure to gluco corticoid in utero [22], The developmental window for this effect is unknown, but the direct hypertensive actions of cortisol in fetal sheep occur in the last trimester [8] and the multiple effects of dexamethasone in late rat gestation [23][24][25] suggest this time may be important. The mecha nisms of hypertension are also unclear.…”

Section: Introductionmentioning

confidence: 99%

Dexamethasone in the Last Week of Pregnancy Attenuates Hippocampal Glucocorticoid Receptor Gene Expression and Elevates Blood Pressure in the Adult Offspring in the Rat

et al. 1996

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Human epidemiological data show a strong association between low birth weight and hypertension in adulthood, an effect that has been ascribed to ‘fetal programming’. In rats, fetoplacental exposure to maternally administered dexamethasone throughout gestation reduces birth weight and produces hypertensive adult offspring, though the mechanism is unclear. Pre- and postnatal stress programmes hypothalamic-pituitary-adrenal (HPA) axis responses throughout the lifespan, an effect thought to be mediated via permanent effects on glucocorticoid receptor (GR) and/or mineralocorticoid receptor (MR) gene expression in the hippocampus. Corticosteroids also have specific central effects on blood pressure control mediated by GR and MR. This study investigated corticosterone (CORT) responses to restraint stress and GR and MR gene expression in areas of the brain postulated to mediate the central effects of corticosteroids on (i) HPA axis suppression (hippocampus), and (ii) blood pressure (organ vasculosum of the lamina terminalis (OVLT), sub-commissural organ, area postrema and nucleus tractus solitarius). Pregnant Wistar rats received dexamethasone (100 µg/kg·day^–1) or vehicle on days 15–20 of gestation. This reduced birth weight by 11 %. When the offspring were 16 weeks old, blood pressure was recorded directly and plasma CORT measured basally (AM) and after 30 min restraint. GR and MR mRNA expression were determined by in situ hybridization. Blood pressure was significantly elevated in the adult offspring of dexamethasone-treated pregnancies (dexamethasone 144 ± 2/125 ± 2 mm Hg vs. control 133 ± 2.7/ 112 ± 2.8 mm Hg; both p < 0.01). Offspring of dexamethasone-treated pregnancies had increased basal plasma CORT (155 ± 29 nmol/l) compared to offspring of controls (79 ± 15 nmol/l, p < 0.05), but the CORT response to stress was similar. Hippocampal neuronal GR mRNA expression was significantly lower in the offspring of dexamethasone-treated pregnancies (dentate gyrus 20% lower, CA1 15% lower; p < 0.01). Similarly, hippocampal MR gene expression was decreased in CA1 and CA2 by 24 and 25%, respectively (p < 0.05). No differences in GR or MR mRNA expression were found in the OVLT, subcommissural organ, area postrema or nucleus tractus solitarius. These findings suggest that glucocorticoid excess in the last trimester of rat pregnancy (i) is sufficient to programme offspring hypertension; (ii) also increases basal plasma CORT levels, and (iii) permanently attenuates GR and MR mRNA expression in specific hippocampal subfields. This, if translated into protein, may reduce sensitivity to glucocorticoid feedback and thus contribute to the CORT excess. However, hypertension in this model is unlikely to be mediated by similar changes in GR or MR gene expression in the examined areas of the brain putatively involved in the more direct central regulation of blood pressure.

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Prenatal dexamethasone administration disrupts the pattern of cellular development in rat lung

Cited by 30 publications

References 10 publications

Glucocorticoids and the Development of Neuronal Function: Effects of Prenatal Dexamethasone Exposure on Central Noradrenergic Activity

Glucocorticoids and the Development of Neuronal Function: Effects of Prenatal Dexamethasone Exposure on Central Noradrenergic Activity

Influence of Postnatally Administered Glucocorticoids on Rat Lung Growth

Dexamethasone in the Last Week of Pregnancy Attenuates Hippocampal Glucocorticoid Receptor Gene Expression and Elevates Blood Pressure in the Adult Offspring in the Rat

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