Rat lung polycholorinated biphenyl-binding protein: effect of glucocorticoids on the expression of the Clara cell-specific protein during fetal development.
Certain metabolites of polychlorinated biphenyls (PCBs) are retained in the Clara cells and in the airway lumen of rodent lung due to their interaction with a secretory 13-kDa protein. The expression of this Clara cell-specific, PCB-binding protein (PCB-BP) during the fetal development of the rat lung was studied by means of ligand binding and a monospecific antiserum. The PCB-BP and specific 4,4'-bis([3H]methylsulfony)-2,2',5,5'-tetrachlorobiphenyl binding was first detected on gestational Day 19 and subsequently the levels of PCB-BP and specific ligand binding increased as a function of gestational age. The start site of transcription for the rat PCB-BP gene was determined by primer extension analysis and the information thus obtained was used to develop a quantitative assay for the corresponding mRNA based on solution hybridization and S1 nuclease mapping. The appearance of PCB-BP mRNA during fetal lung development preceded the detection of immunoreactive protein and ligand binding by 1 day. By Day 21, the level of PCB-BP mRNA was 15 ng/100 micrograms total lung RNA which is approximately 30-40% of adult levels. In utero exposure to the synthetic glucocorticoid betamethasone was shown to increase specific 4,4'-bis([3H]methylsulfonyl)2,2',5,5'- tetrachlorobiphenyl binding, PCB-BP protein, and PCB-BP mRNA if administered from gestational Day 18 and onward. By Days 21-22, glucocorticoid treatment resulted in a two- to threefold increase in the levels of specific ligand binding, immunoreactivity, and mRNA, i.e., to approximately adult levels.
Nord
M
M
Department of Medical Nutrition, Karolinska Institutet, Huddinge University Hospital, Sweden.
Andersson
O
O
Brönnegård
M
M
Lund
J
J
D000818:Animals; D001483:Base Sequence; D001623:Betamethasone / Q000494:pharmacology*; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D005314:Embryonic and Fetal Development; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D005865:Gestational Age; D008168:Lung / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D011247:Pregnancy; D011506:Proteins; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D014598:Uteroglobin
D002352:Carrier Proteins; D009838:Oligodeoxyribonucleotides; D011506:Proteins; D012333:RNA, Messenger; C556391:Scgb1a1 protein, rat; D014598:Uteroglobin; D001623:Betamethasone