Effect of gestational age and retinol (vitamin A) deficiency on fetal rat lung nuclear retinoic acid receptors.
Retinol, or one of its metabolites such as retinoic acid (RA), is an important factor in the differentiation and maintenance of integrity of lung epithelium. Retinol deficiency in rats induces morphologic changes in respiratory tract epithelial cells that are histologically similar to those found in human premature infants with bronchopulmonary dysplasia. The exact mechanism of retinoid action in cellular growth and differentiation is not understood, but recently investigators have focused on mechanisms mediated by nuclear RA receptors (RAR). The role of these RAR as regulators of retinoid function is being studied in adult animal tissues and malignant cell lines, but little is known about RAR in developing fetal lung tissue. The purpose of this study was to determine the effect of gestational age and vitamin A deficiency on fetal rat lung nuclear RAR. RAR were also assayed in vitamin A control and vitamin A-deficient adult rat lung. A competitive binding assay and size exclusion HPLC separation were used to quantitate total RAR-specific binding. Binding analysis revealed a single class of receptor binding sites with high affinity (kd approximately 10(-9) M) for RA and RAR saturation at 2-5 nM RA. Specific binding of lung RAR in rat fetuses at 18 d gestation was two to three times greater than in fetuses at 20-21 d gestation, newborn pups, or adults. Western blot analysis revealed a predominance of RAR-beta receptors in fetal lung. Lungs from vitamin A-deficient fetuses demonstrated up-regulation of nuclear RAR.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pediatrics, University of Wisconsin, Madison 53715.
K R
KR
McMenamy
R D
RD
Zachman
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D005260:Female; D005325:Fetal Organ Maturity; D005333:Fetus / Q000378:metabolism*; D005865:Gestational Age; D007700:Kinetics; D008168:Lung / Q000196:embryology / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D018168:Receptors, Retinoic Acid; D014212:Tretinoin / Q000378:metabolism*; D015854:Up-Regulation; D014802:Vitamin A Deficiency / Q000378:metabolism*
D002352:Carrier Proteins; D018168:Receptors, Retinoic Acid; D014212:Tretinoin