Glucocorticoids regulate expression of the fatty acid synthase gene in fetal rat type II cells.
Fatty acids are integral components of pulmonary surfactant, a mixture of phospholipids and specific proteins that lines the alveolar surface and is essential for normal lung function. There are developmental increases in fatty acid biosynthesis and surfactant production in late-gestation fetal lung, and both processes are accelerated by glucocorticoids. Fatty acid synthase (FAS) is a key enzyme in de novo fatty acid biosynthesis, and increased FAS activity is responsible for the developmental and hormone-induced increases in fatty acid biosynthesis in fetal lung. Using cultured fetal lung explants, it has been reported that dexamethasone (Dex) increases FAS activity, protein content, mRNA content and rate of transcription. However, FAS expression has not been measured in isolated type II cells, the cellular source of surfactant within the lung. In the present study we measured parameters of FAS expression in type II cells isolated from the lungs of Dex-treated rats. Pregnant rats were injected with Dex or saline on days 18 and 19 of gestation and the fetuses delivered on day 20. Type II cells and fibroblasts were then isolated from the fetal lungs. Dex increased FAS activity, protein content, mRNA content and rate of transcription in the type II cells but not in the fibroblasts. Increased FAS expression in fetal type II cells in response to Dex is consistent with a critical role for FAS in the biosynthesis of lung surfactant.
Beneke
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Division of Perinatal Medicine, Department of Pediatrics, Yale University School of Medicine, P.O. Box 208064, New Haven, CT 06520-8064, , USA
Rooney
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SA
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology; D064429:Fatty Acid Synthases / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005865:Gestational Age; D005938:Glucocorticoids / Q000494:pharmacology* / Q000502:physiology; D008168:Lung / Q000196:embryology / Q000378:metabolism*; D011247:Pregnancy; D011663:Pulmonary Surfactants / Q000096:biosynthesis; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats
D005938:Glucocorticoids; D011663:Pulmonary Surfactants; D012333:RNA, Messenger; D003907:Dexamethasone; D064429:Fatty Acid Synthases