title: Spatial and temporal expression of glucocorticoid, retinoid, and thyroid hormone receptors is not altered in lungs of congenital diaphragmatic hernia.
abstract: The degree of associated pulmonary hypoplasia and persistent pulmonary hypertension are major determination factors for survival in congenital diaphragmatic hernia (CDH) patients. Glucocorticoids, thyroid hormone, and vitamin A have been shown to be involved in human lung development. To determine their therapeutic potential in hypoplastic lungs of CDH patients, the temporal and spatial expression of glucocorticoid receptor, thyroid hormone receptors, retinoic acid receptors, and retinoid X receptors were evaluated in lungs of CDH patients, hypoplastic lungs from other causes, and normal lungs. As a series of supportive experiments, the expressions of these receptors were analyzed in lungs of nitrofen-induced CDH rats. Immunohistochemistry (human and rat) and in situ hybridization (rat) demonstrated no overt difference between CDH, hypoplastic, and control lungs, either in the localization nor the timing of the first expression of all analyzed receptors. The mRNA expression of each receptor was detected in all human CDH lungs by quantitative PCR. Our results suggest that, as far as receptors are concerned, hypoplastic lungs of fetuses and newborns with CDH are potentially as responsive to glucocorticoids, thyroid hormone, and retinoic acid as the lungs of normal children.
authors.affiliation: Department of Pediatric Surgery, Sophia Children's Hospital, Erasmus MC-University Medical Center, 3015 GJ, Rotterdam, the Netherlands.
authors.forename: Prapapan
authors.initials: P
authors.lastname: Rajatapiti
authors.forename: Richard
authors.initials: R
authors.lastname: Keijzer
authors.forename: Pietjan E
authors.initials: PE
authors.lastname: Blommaart
authors.forename: Wouter H
authors.initials: WH
authors.lastname: Lamers
authors.forename: Ronald R
authors.initials: RR
authors.lastname: DE Krijger
authors.forename: Theo J
authors.initials: TJ
authors.lastname: Visser
authors.forename: Dick
authors.initials: D
authors.lastname: Tibboel
authors.forename: Robbert
authors.initials: R
authors.lastname: Rottier
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D006548:Hernia, Diaphragmatic / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism*; D065630:Hernias, Diaphragmatic, Congenital; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000378:metabolism* / Q000473:pathology; D010647:Phenyl Ethers; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000235:genetics / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D047488:Retinoid X Receptors / Q000235:genetics / Q000378:metabolism*
chemical_list: D010647:Phenyl Ethers; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D047488:Retinoid X Receptors; C007350:nitrofen