Glucocorticoid stimulation of fatty-acid synthase gene transcription in fetal lung: antagonism by retinoic acid.
Glucocorticoid hormones are known to stimulate the rate of fatty acid biosynthesis and to increase the activity and mRNA level of fatty-acid synthase (FAS) in late gestation fetal lung. We have now examined the effect of dexamethasone on FAS transcription in fetal rat lung. Explants of 19-day fetal rat lung cultured for 48 h in serum-free medium were exposed to dexamethasone (10(-7) M) for various time periods. Nuclei were isolated, and the rate of [32P]UTP incorporation into FAS and gamma-actin RNA transcripts was measured by transcription-elongation assay. Dexamethasone increased FAS transcription but had no effect on that of actin. The maximum effect of the hormone, approximately threefold increase, was observed 1-2 h after addition of the hormone but was still apparent up to 48 h. FAS transcription but not that of actin was inhibited by cycloheximide and puromycin in both control and dexamethasone-treated cultures. However, the stimulatory effect of the hormone was not significantly reduced by the inhibitors. Retinoic acid antagonized the stimulatory effects of dexamethasone on FAS activity, mRNA content as measured by Northern analysis, mass as measured by Western blotting, and rate of transcription. The effect of retinoic acid was dependent on concentration in the relatively narrow range of 5 x 10(-6) to 5 x 10(-4) M. These data show that glucocorticoids stimulate transcription of the FAS gene in late gestation fetal rat lung, that normal transcription of the FAS gene is dependent on ongoing protein synthesis, and that glucocorticoid stimulation of FAS gene expression is antagonized by retinoic acid.
Xu
Z X
ZX
Department of Pediatrics, Yale University, School of Medicine, New Haven, Connecticut 06520, USA.
Viviano
C J
CJ
Rooney
S A
SA
D000818:Animals; D003907:Dexamethasone / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D064429:Fatty Acid Synthases / Q000819:agonists / Q000235:genetics* / Q000378:metabolism; D005333:Fetus / Q000502:physiology*; D015870:Gene Expression / Q000187:drug effects; D008168:Lung / Q000196:embryology*; D012313:RNA / Q000378:metabolism; D051381:Rats / Q000196:embryology; D014158:Transcription, Genetic / Q000187:drug effects*; D014212:Tretinoin / Q000494:pharmacology*
D014212:Tretinoin; D012313:RNA; D003907:Dexamethasone; D064429:Fatty Acid Synthases