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Expression of Glucocorticoid, Retinoid, and Thyroid Hormone Receptors during Human Lung Development

Department of Pediatric Surgery (P.R., R.R., D.T.), Erasmus MC-Sophia Children’s Hospital-University Medical Center, 3015 GJ Rotterdam, The Netherlands; Department of Internal Medicine (P.R., M.H.A.K., T.J.V.), Department of Pathology (R.R.d.K.), Josephine Nefkens Institute, and Department of Cell Biology and Genetics (R.R.), Erasmus MC-University Medical Center, 3015 GJ Rotterdam, The Netherlands; and Department of Surgery (P.R.), Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand

Address all correspondence and requests for reprints to: Dick Tibboel, M.D., Ph.D., Department of Pediatric Surgery, Erasmus MC-Sophia Children’s Hospital, University Medical Center, Dr Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands. E-mail: j.illsley{at}erasmusmc.nl.

Context: Although glucocorticoid hormone, thyroid hormone, and retinoic acid play important roles in fetal development, the expression of their receptors in human lung is still unknown.

Objective: The aim of this study was to investigate the ontogeny of glucocorticoid receptor (GR), thyroid hormone receptors (TRs), retinoic acid receptors (RARs), and retinoid X receptors (RXRs) mRNA expression in human lungs.

Design: Lungs from human fetuses and neonates (13.5–41 wk gestation; n = 20) as well as adults (n = 5) were analyzed by real-time PCR to monitor the ontogeny of mRNA expression for each receptor. In addition, immunohistochemistry was performed to show the cellular distribution of the different receptors.

Results: The expression of GR, TRs, RARs, and RXRs was already detected in the earliest developmental stages analyzed. There was no significant difference in mRNA expression between developmental groups for any of the genes studied. However, for fetal and neonatal samples, there were positive correlations between gestational age and mRNA expression for RAR (r = 0.665; P = 0.001), RXR (r = 0.444; P = 0.050), and RXR (r = 0.464; P = 0.039). Immunohistochemical studies showed the presence of GR, TRs, RARs, and RXRs in the nuclei of both epithelial and mesenchymal cells, albeit more pronounced in epithelium of larger airways.

Conclusions: The detection of GR, TRs, RARs, and RXRs expression in human lung as early as 13.5 wk gestation implies an early potential for therapeutic or toxic effects by exogenous analogs or by excess of endogenous ligands.

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