| Title: |
Both thyroid hormone receptor (TR)beta 1 and TR beta 2 isoforms contribute to the regulation of hypothalamic thyrotropin-releasing hormone. |
| Authors: |
Dupre, Sm; Guissouma H, *; Flamant, F.; Seugnet I, *; Scanlan, Ts; Baxter, Jd; Samarut, J.; Demeneix Ba., *; Becker N, * |
| Contributors: |
Evolution des régulations endocriniennes (ERE); Muséum national d'Histoire naturelle (MNHN)-Centre National de la Recherche Scientifique (CNRS) |
| Source: |
ISSN: 0013-7227 ; Endocrinology ; https://hal.archives-ouvertes.fr/hal-00096392 ; Endocrinology, Endocrine Society, 2004, May;145(5), pp.2337-45. |
| Publisher Information: |
HAL CCSD; Endocrine Society |
| Publication Year: |
2004 |
| Collection: |
Archive ouverte HAL (Hyper Article en Ligne, CCSD - Centre pour la Communication Scientifique Directe) |
| Description: |
Thyroid hormones (TH) are essential regulators of vertebrate development and metabolism. Central mechanisms governing their production have evolved, with the beta-TH receptor (TRbeta) playing a key regulatory role in the negative feedback effects of circulating TH levels on production of hypothalamic TRH and hypophyseal TSH. Both TRbeta-isoforms (TRbeta1 and TRbeta2) are expressed in the hypothalamus and pituitary. However, their respective roles in TH-dependent transcriptional regulation of TRH are undefined. We confirmed the preferential role of TRbeta vs. TRalpha isoforms in TRH regulation in wild-type mice in vivo by using the TRbeta preferential agonist GC-1. We next determined the effects of tissue-specific rescue of TRbeta1 and TRbeta2 isoforms by somatic gene transfer in hypothalami of TRbeta null (TRbeta(-/-)) mice. TH-dependent TRH transcriptional repression was impaired in TRbeta(-/-) mice, but was restored by cotransfection of either TRbeta1 or TRbeta2 into the hypothalamus. TRbeta1, but not TRbeta2, displayed a role in ligand-independent activation. In situ hybridization was used to examine endogenous TRH expression in the paraventricular nucleus of the hypothalamus of TRbeta(-/-) or TRalpha null (TRalpha(o/o)) mice under different thyroid states. In contrast to published data on TRbeta2(-/-) mice, we found that both ligand-independent TRH activation and ligand-dependent TRH repression were severely impaired in TRbeta(-/-) mice. This study thus provides functional in vivo data showing that both TRbeta1 and TRbeta2 isoforms have specific roles in regulating TRH transcription. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
hal-00096392; https://hal.archives-ouvertes.fr/hal-00096392 |
| Availability: |
https://hal.archives-ouvertes.fr/hal-00096392 |
| Accession Number: |
edsbas.57C1442B |
| Database: |
BASE |