Expression of glucocorticoid, retinoid, and thyroid hormone receptors during human lung development.
BACKGROUND
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)alpha, thyroid hormone receptors (TRs), retinoic acid receptors (RARs), and retinoid X receptors (RXRs) mRNA expression in human lungs.


METHODS
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 GRalpha, 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 RARalpha (r = 0.665; P = 0.001), RXRalpha (r = 0.444; P = 0.050), and RXRgamma (r = 0.464; P = 0.039). Immunohistochemical studies showed the presence of GRalpha, 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 GRalpha, 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.
Rajatapiti
Prapapan
P
Department of Pediatric Surgery, Erasmus MC-Sophia Children's Hospital, University Medical Center, Dr Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands.
Kester
Monique H A
MH
de Krijger
Ronald R
RR
Rottier
Robbert
R
Visser
Theo J
TJ
Tibboel
Dick
D
D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007231:Infant, Newborn; D008168:Lung / Q000196:embryology* / Q000378:metabolism*; D011247:Pregnancy; D012333:RNA, Messenger / Q000032:analysis; D011965:Receptors, Glucocorticoid / Q000032:analysis / Q000235:genetics*; D018168:Receptors, Retinoic Acid / Q000032:analysis / Q000235:genetics*; D011988:Receptors, Thyroid Hormone / Q000032:analysis / Q000235:genetics*; D047488:Retinoid X Receptors / Q000032:analysis / Q000235:genetics*
D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D047488:Retinoid X Receptors; C411470:glucocorticoid receptor alpha