Glucocorticoid receptor expression in fetal non-human primate lung

Abstract

The purpose of this study was to use a unique set of phosphorylation state–specific antibodies to examine the activation of glucocorticoid receptors in steroid-treated and untreated fetal baboon lung. Pregnant baboons were randomized to receive either betamethasone at a dosing regimen of 175 μg/kg/day or saline for 48 hours. Cesarean deliveries were performed 12 hours after the last dose of either treatment or placebo, corresponding to a gestational age of 136 days (comparable to 28-29 weeks' gestation in humans). Immunohistochemistry was performed on serial sections of paraffin-embedded blocks of fetal lung biopsies and stained with antibodies for total glucocorticoid receptor (GR) and for phosphorylated GR at serine-226. GR expression was quantified by sampling three parenchymal fields (mediastinal, middle, peripheral) using 100× magnification with oil immersion. Cell counts were performed and positively staining cells were recorded as a percentage of total cells per field. The examiner was blinded to treatment conditions. Subjectively, fetal lung tissue from steroid-treated animals exhibited increased total GR expression. There was a notable gradient of GR expression (higher in the periphery, lower in the mediastinal area). Mean GR expression in the fetal lungs from steroid-treated animals was 63% of cells versus 55.8% in saline-treated (t-test, P = 0.04). Recycling GR (phosphorylated GR at serine-226) activity was not statistically significant between the two groups. Antenatal glucocorticoid treatment is associated with increased total GR expression in the fetal baboon lung model. This contrasts greatly with low levels of GR expression in human adult lung and suggests that GR expression may be downregulated during the transition from fetal to postnatal development.