Journal article
Critical role for thyroid hormone receptor β2 in the regulation of paraventricular thyrotropin-releasing hormone neurons
The Journal of clinical investigation, Vol.107(8), pp.1017-1023
04/15/2001
DOI: 10.1172/JCI10858
PMID: 11306605
Abstract
Thyroid hormone thyroxine (T\n4\n) and tri-iodothyronine (T\n3\n) production is regulated by feedback inhibition of thyrotropin (TSH) and thyrotropin-releasing hormone (TRH) synthesis in the pituitary and hypothalamus when T\n3\nbinds to thyroid hormone receptors (TRs) interacting with the promoters of the genes for the TSH subunit and TRH. All of the TR isoforms likely participate in the negative regulation of TSH production in vivo, but the identity of the specific TR isoforms that negatively regulate TRH production are less clear. To clarify the role of the TR-β2 isoform in the regulation of TRH gene expression in the hypothalamic paraventricular nucleus, we examined preprothyrotropin-releasing hormone (prepro-TRH) expression in mice lacking the TR-β2 isoform under basal conditions, after the induction of hypothyroidism with propylthiouracil, and in response to T\n3\nadministration. Prepro-TRH expression was increased in hypothyroid wild-type mice and markedly suppressed after T\n3\nadministration. In contrast, basal TRH expression was increased in TR-β2–null mice to levels seen in hypothyroid wild-type mice and did not change significantly in response to induction of hypothyroidism or T\n3\ntreatment. However, the suppression of TRH mRNA expression in response to leptin reduction during fasting was preserved in TR-β2–null mice. Thus TR-β2 is the key TR isoform responsible for T\n3\n-mediated negative-feedback regulation by hypophysiotropic TRH neurons.
Details
- Title: Subtitle
- Critical role for thyroid hormone receptor β2 in the regulation of paraventricular thyrotropin-releasing hormone neurons
- Creators
- E. Dale Abel - Division of Endocrinology, Metabolism and Diabetes and Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, Utah, USARexford S Ahima - Division of Endocrinology, Metabolism and Diabetes and Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, Utah, USAMary-Ellen Boers - Division of Endocrinology, Metabolism and Diabetes and Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, Utah, USAJoel K Elmquist - Division of Endocrinology, Metabolism and Diabetes and Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, Utah, USAFredric E Wondisford - Division of Endocrinology, Metabolism and Diabetes and Program in Human Molecular Biology and Genetics, University of Utah, Salt Lake City, Utah, USA
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.107(8), pp.1017-1023
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/JCI10858
- PMID
- 11306605
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 04/15/2001
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Fraternal Order of Eagles Diabetes Research Center; Biochemistry and Molecular Biology; Endocrinology and Metabolism; Internal Medicine
- Record Identifier
- 9984024400702771
Metrics
9 Record Views