Glucocorticoid regulation of surfactant‐associated proteins in rabbit fetal lung in vivo

Abstract

The effects of a maternally administered synthetic glucocorticoid, betamethasone, on the levels of mRNA for the surfactant proteins SP-A, SP-B, and SP-C and on the levels of SP-A protein were investigated in day 27 gestational age rabbit fetal lung tissue. Betamethasone administration to the pregnant rabbit caused approximately a twofold increase in the fetal lung level of SP-A protein and a threefold increase in fetal lung SP-A mRNA levels when compared to levels in fetuses obtained from saline-treated or uninjected animals. SP-B mRNA was increased fourfold in fetal lung tissue obtained from glucocorticoid-treated pregnant does when compared to levels in fetuses of uninjected pregnant does. However, SP-B mRNA levels in fetal lung tissue from saline-injected controls were also significantly elevated, approximately twofold, when compared to fetal lung SP-B mRNA levels in the uninjected control condition. SP-C mRNA levels in lung tissue of fetuses from both saline-injected and betamethasone-injected pregnant does were increased similarly, approximately twofold, over SP-C mRNA levels in fetal lung tissue obtained from uninjected control does. These data are suggestive that betamethasone treatment increases fetal lung SP-A and SP-B mRNA levels and that maternal stress alone can increase the expression of SP-B and SP-C mRNA in rabbit fetal lung tissue. Using in situ hybridization, SP-A mRNA was shown to be present primarily in alveolar type II cells in fetuses of control and saline-injected does. However, SP-A mRNA was easily detected in both alveolar type II cells and bronchiolar epithelial cells of rabbit fetal lung tissue following maternal betamethasone treatment. In contrast, SP-B and SP-C mRNA were present only in alveolar type II cells of lung tissue obtained from fetuses of control, saline, or betamethasone-treated does. Thus maternal administration of glucocorticoids increased SP-A protein as well as SP-A and SP-B mRNA levels in rabbit fetal lung tissue. SP-A mRNA was localized to both alveolar type II cells and in smaller amounts in bronchiolar epithelial cells of rabbit fetal lung tissue. However, SP-B and SP-C mRNA were detected only in alveolar type II cells.

Preterm rabbit lung tissue mechanics: Maturational changes and effect of antenatal steroids

“…In a study by Malee and Marotta, 21 stress by dehydration of pregnant does did result in a measurable increase in fetal cortisol synthesis and excretion. Durham et al 22 documented a similar increase in SP-B and SP-C mRNA levels in rabbit pups at 27 days GA exposed to either BM ¼ 0.2 mg/kg or placebo. Since we did not anticipate such placebo effect, we did not collect maternal nor fetal blood samples to clarify this issue.…”

Oxidative stress after antenatal betamethasone: Acute downregulation of glutathione peroxidase-3

“…Antenatal GC produce a number of rapid and transient effects in the fetus, notably a surge in surfactant protein expression in the lungs [24], which is the basis for its administration. Early and transitory side-effects of the treatment include insulin resistance and nutrient catabolism [3,12], alterations in the fetal heart rate pattern [5][6][7], and impairment of the cardiovascular and endocrine responses to hypoxemia [10,11].…”

Antenatal Glucocorticoid Therapy Accelerates ATP Production With Creatine Kinase Increase in the Growth-Enhanced Fetal Rat Heart

“…JC-1 uptake was significantly increased in the 21-day fetal and 1-day-old neonatal groups that received DEX (1.0×10 6 and 1.4×10 6 fluorescence unit/mg protein, respectively) compared with the respective controls (4.7×10 5 and 6.0×10 5 fluorescence units/mg protein, respectively). The 21-day fetal and 1-dayold neonatal groups administered DEX 2 mg/kg thus showed an increase in JC-1 uptake of approximately 2.0-2.5-fold.…”

“…5 Durham et al found that antenatal GC administration leads to the sufficient production of surfactant and subsequent maturation of lung tissue. 6 …”