We have investigated the effects of
retinoids,
vitamin D and
thyroid hormone on the levels of
retinoic acid receptor (RAR)alpha,
RAR beta and
RAR gamma mRNAs in intact animals. Although
vitamin A deficiency caused no significant changes in the levels of RAR alpha and
RAR gamma mRNAs, the level of
RAR beta transcripts was greatly decreased in various tissues of
vitamin A-deficient rats, but was restored rapidly to a normal level after administration of
retinoic acid.
Retinol also restored the
RAR beta mRNA level, but the magnitude and kinetics of the induction differed from those by
retinoic acid. The use of specific inhibitors demonstrated that this autoregulation of
RAR beta gene expression in vivo occurred at the transcriptional level. In addition, from these results it was postulated that the maintenance of the normal
RAR beta mRNA levels seemed to require a threshold serum
retinol concentration (about 25 micrograms/dl). Moreover, we found that administration of
retinol and
retinoic acid to normal rats caused the overexpression of
RAR beta transcripts (2-15-fold) when compared with the control levels of
RAR beta mRNA, although the levels of RAR alpha and
RAR gamma mRNAs were not affected.
Vitamin D and
thyroid hormone did not modulate the levels of RAR transcripts. These findings clearly indicate the specific
ligand regulation of
RAR beta gene expression in intact animals. The altered levels of
RAR beta according to
retinoid status may affect
retinoid-inducible gene expression.