EFFECT OF RETINOID STATUS ON ALPHA, BETA AND GAMMA-RETINOIC ACID RECEPTOR MESSENGER-RNA LEVELS IN VARIOUS RAT-TISSUES

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-mu-g/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.