Positive and negative regulation of retinoid X receptor gene expression by thyroid hormone in the rat. Transcriptional and post-transcriptional controls by thyroid hormone.
The 9-cis-retinoic acid receptors (RXRs), belonging to the members of the steroid/thyroid hormone receptor superfamily, act as auxiliary proteins, heterodimerizing with other nuclear receptors such as retinoic acid receptors (RARs), vitamin D receptor, thyroid hormone receptors, and peroxisome-proliferator activated receptor, thereby transactivating target genes in a ligand-dependent manner. We have previously reported that in the rat, thyroid hormone (TH) positively and negatively regulates the hepatic mRNA levels of RXR beta and RXR gamma, respectively. In the present study, we have tried to elucidate the level at which TH regulates the gene expression of RXR beta and RXR gamma in the rat. A RNA synthesis inhibitor (actinomycin D), but not a protein synthesis inhibitor (cycloheximide), blocked the induction of RXR beta mRNA by TH. On the other hand, none of these drugs inhibited the decrease of RXR gamma mRNA levels caused by TH. Nuclear run-on assays showed that the transcription rate of the RXR beta gene was positively regulated by TH, whereas the transcription of RXR gamma gene was not controlled by TH. Taken together, these results indicate that the gene expression of RXR beta is positively regulated by TH at transcriptional level, while the negative regulation of the RXR gamma gene expression by TH may occur at a post-transcriptional level in intact rat. Thus, the RXR-mediated signal transductions may be modulated in part through TH control of the levels of RXR beta and RXR gamma.
Mano
H
H
Department of Agricultural Chemistry, Faculty of Agriculture, Tokyo University of Agriculture, Japan.
Mori
R
R
Ozawa
T
T
Takeyama
K
K
Yoshizawa
Y
Y
Kojima
R
R
Arao
Y
Y
Masushige
S
S
Kato
S
S
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006321:Heart / Q000187:drug effects; D007037:Hypothyroidism / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D011441:Propylthiouracil / Q000494:pharmacology; D012323:RNA Processing, Post-Transcriptional / Q000187:drug effects / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis* / Q000235:genetics*; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids / Q000378:metabolism*; D014157:Transcription Factors; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*; D014284:Triiodothyronine / Q000494:pharmacology*
D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; D014157:Transcription Factors; D014284:Triiodothyronine; D011441:Propylthiouracil