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. Expla nts of 19-day fetal rat lung cultured for 48 h in serum-free medium we re exposed to dexamethasone (10(-7) M) for various time periods. Nucle i were isolated, and the rate of [P-32]UTP incorporation into FAS and gamma-actin RNA transcripts was measured by transcription-elongation a ssay. Dexamethasone increased FAS transcription but had no effect on t hat of actin. The maximum effect of the hormone, approximately threefo ld 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 dexameth asone-treated cultures. However, the stimulatory effect of the hormone was not significantly reduced by the inhibitors. Retinoic acid antago nized the stimulatory effects of dexamethasone on FAS activity, mRNA c ontent as measured by Northern analysis, mass as measured by Western b lotting, and rate of transcription. The effect of retinoic acid was de pendent on concentration in the relatively narrow range of 5 x 10(-6) to 5 x 10(-4) M. These data show that glucocorticoids stimulate transc ription of the FAS gene in late gestation fetal rat lung, that normal transcription of the FAS gene is dependent on ongoing protein synthesi s, and that glucocorticoid stimulation of FAS gene expression is antag onized by retinoic acid.