POSITIVE AND NEGATIVE REGULATION OF RETINOID X-RECEPTOR GENE-EXPRESSION BY THYROID-HORMONE IN THE RAT - TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL CONTROLS BY THYROID-HORMONE
H. Mano et al., POSITIVE AND NEGATIVE REGULATION OF RETINOID X-RECEPTOR GENE-EXPRESSION BY THYROID-HORMONE IN THE RAT - TRANSCRIPTIONAL AND POSTTRANSCRIPTIONAL CONTROLS BY THYROID-HORMONE, The Journal of biological chemistry, 269(3), 1994, pp. 1591-1594
The 9-cis-retinoic acid receptors (RXRs), belonging to the members of
the steroid/thyroid hormone receptor superfamily, act as auxiliary pro
teins, heterodimerizing with other nuclear receptors such as retinoic
acid receptors (RARs), vitamin D receptor, thyroid hormone receptors,
and peroxisome-proliferator activated receptor, thereby transactivatin
g target genes in a ligand-dependent manner. We have previously report
ed that in the rat, thyroid hormone (TH) positively and negatively reg
ulates the hepatic mRNA levels of RXRbeta and RXRgamma, respectively.
In the present study, we have tried to elucidate the level at which TH
regulates the gene expression of RXRbeta and RXRgamma in the rat. A R
NA synthesis inhibitor (actinomycin D), but not a protein synthesis in
hibitor (cycloheximide), blocked the induction of RXRbeta mRNA by TH.
On the other hand, none of these drugs inhibited the decrease of RXRga
mma mRNA levels caused by TH. Nuclear run-on assays showed that the tr
anscription rate of the RXRbeta gene was positively regulated by TH, w
hereas the transcription of RXRgamma gene was not controlled by TH. Ta
ken together, these results indicate that the gene expression of RXRbe
ta is positively regulated by TH at transcriptional level, while the n
egative regulation of the RXRgamma gene expression by TH may occur at
a post-transcriptional level in intact rat. Thus, the RXR-mediated sig
nal transductions may be modulated in part through TH control of the l
evels of RXRbeta and RXRgamma.