AJP - Lung Cellular and Molecular Physiology, Vol 268, Issue 4 683-L690, Copyright © 1995 by American Physiological Society
Glucocorticoid stimulation of fatty-acid synthase gene transcription in fetal lung: antagonism by retinoic acid
Z. X. Xu, C. J. Viviano and S. A. Rooney
Department of Pediatrics, Yale University, School of Medicine, New Haven, Connecticut 06520, USA.
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.
