RXR acts as a coregulator in the regulation of genes of the hypothalamo-pituitary axis by thyroid hormone receptors.
Thyroid hormone receptors (TRs) often modulate transcriptional activity of target genes by heterodimerization with the 9-cis retinoic acid receptor (RXR). On positive thyroid response elements (TREs), RXR favors binding of the TR-RXR complex to DNA and stimulates transcription. RXR action on negative TREs is unclear. Furthermore, the single half-site configuration of many negative TREs does not favor the binding of a classic TR-RXR heterodimer. In a comparative study using CV-1 cells (relatively RXR- and TR-deficient) and JEG-3 cells (relatively TR-deficient), we demonstrate the importance of RXR in the negative transcriptional regulation of genes of the hypothalamo-pituitary axis by tri-iodothyronine. While RXR has variable effects on ligand-independent activation produced by TRs, it was required for efficient ligand-dependent repression of the TRH gene for TRalpha1 and TRbeta1 and of the TSH genes by all TRs. Using different RXR constructs we also observed the importance of the C-terminus of RXR but not of the N-terminus nor the DNA-binding domain, in the potentiation of negative regulation. We thus suggest that, with regard to negative regulation of the TRH and TSH genes by thyroid hormones, RXR behaves more like a cofactor than a classic heterodimerization partner.
Department of Physiology and Medicine, Division of Endocrinology, Faculty of Medicine, University of Sherbrooke, CHUS, 3001, 12th Avenue North, Sherbrooke, Quebec, Canada J1H 5N4.
L
L
Laflamme
G
G
Hamann
N
N
Messier
S
S
Maltais
M-F Langlois
D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D005786:Gene Expression Regulation / Q000502:physiology*; D007030:Hypothalamo-Hypophyseal System; D010957:Plasmids; D011233:Precipitin Tests; D011485:Protein Binding; D018168:Receptors, Retinoic Acid / Q000502:physiology*; D011988:Receptors, Thyroid Hormone / Q000502:physiology*; D047488:Retinoid X Receptors; D014157:Transcription Factors / Q000502:physiology*
D018168:Receptors, Retinoic Acid; D011988:Receptors, Thyroid Hormone; D047488:Retinoid X Receptors; D014157:Transcription Factors