Effect of retinoid status on α, β and γ retinoic acid receptor mRNA levels in various rat tissues

Abstract

We have investigated the effects of retinoids, vitamin D and thyroid hormone on the levels of retinoic acid receptor (RAR)α, RARβ and RARγ mRNAs in intact animals. Although vitamin A deficiency caused no significant changes in the levels of RARα and RARγ mRNAs, the level of RARβ 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 RARβ 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 RARβ gene expression in vivo occurred at the transcriptional level. In addition, from these results it was postulated that the maintenance of the normal RARβ mRNA levels seemed to require a threshold serum retinol concentration (about 25μg/dl). Moreover, we found that administration of retinol and retinoic acid to normal rats caused the overexpression of RARβ transcripts (2-15-fold) when compared with the control levels of RARβ mRNA, although the levels of RARα and RARγ 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 RARβ gene expression in intact animals. The altered levels of RARβ according to retinoid status may affect retinoid-inducible gene expression.