773: Corticotrophin releasing hormone (CRH) is related to pulmonary maturation in human fetal lung

Antenatal glucocorticoids promote lung maturity, but their molecular mechanisms are poorly understood. We previously made the novel observation that CRH is present in the murine fetal lung and is modified in its expression following antenatal glucocorticoids. Our current objective was to expand the translational significance of our studies by identifying the temporal and spatial expression of CRH in human fetal lung, then correlate these findings with those in our Erk3-/-murine model. Protein expression of CRH and SFTPB was quantitated by immunohistochemistry (IHC) from midtrimester human fetal lung samples (n=5, 18-22 weeks). Ten random high-power fields/slide were analyzed using Image ProPlus, using a grading scale from 0 to 5 that identifies number of cells per HPF. Two negative controls for each slide were utilized. Data were analyzed by ANOVA, using the statistical software package SPSS v 11.5 with minimal significance designated at p<0.05. In order to derive functional significance, CRH levels following antenatal glucocorticoids and post-natal surfactant were studied in our Erk3-/- murine model of RDS. Improved survival was associated with CRH attenuation and following antenatal dexa administration followed by postnatal surfactant (Figure A). Quantitation of protein expression by IHC demonstrated that CRH is prevalent in human lungs through the mid trimester. CRH increases as gestational ages advances from 18-22 weeks with a significant increased expression from 18-22 weeks (p<0.01), 19-22 weeks (p<0.001) and 20-22 weeks (p<0.001). For CRH, both epithelial and interstitial cells are positive with a trend to be more proximal in the case of epithelial cells. SFTPB expression is variable through the mid-trimester (Figure B). We demonstrate for the first time that CRH is present in human fetal lung tissue, increasing towards the cusp of viability. Taken together, these findings are consistent with a likely key role for CRH as a molecular mediator of pulmonary maturation.