Journal article
Divergent roles for thyroid hormone receptor β isoforms in the endocrine axis and auditory system
The Journal of clinical investigation, Vol.104(3), pp.291-300
08/01/1999
DOI: 10.1172/JCI6397
PMCID: PMC408418
PMID: 10430610
Abstract
Thyroid hormone receptors (TRs) modulate various physiological functions in many organ systems. The TR alpha and TR beta isoforms are products of 2 distinct genes, and the beta 1 and beta 2 isoforms are splice variants of the same gene. Whereas TR alpha 1 and TR beta 1 are widely expressed, expression of the TR beta 2 isoform is mainly limited to the pituitary, triiodothyronine-responsive TRH neurons, the developing inner ear, and the retina. Mice with targeted disruption of the entire TR beta locus (TR beta-null) exhibit elevated thyroid hormone levels as a result of abnormal central regulation of thyrotropin, and also develop profound hearing loss. To clarify the contribution of the TR beta 2 isoform to the function of the endocrine and auditory systems in vivo, we have generated mice with targeted disruption of the TR beta 2 isoform. TR beta 2-null mice have preserved expression of the TR alpha and TR beta 1 isoforms. They develop a similar degree of central resistance to thyroid hormone as TR beta-null mice, indicating the important role of TR beta 2 in the regulation of the hypothalamic-pituitary-thyroid axis. Growth hormone gene expression is marginally reduced. In contrast, TR beta 2-null mice exhibit no evidence of hearing impairment, indicating that TR beta 1 and TR beta 2 subserve divergent roles in the regulation of auditory function.
Details
- Title: Subtitle
- Divergent roles for thyroid hormone receptor β isoforms in the endocrine axis and auditory system
- Creators
- E. Dale AbelMary-Ellen BoersCarmen Pazos-MouraEgberto MouraHelen KaulbachMarjorie ZakariaBradford LowellSally RadovickM. Charles LibermanFredric Wondisford
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.104(3), pp.291-300
- DOI
- 10.1172/JCI6397
- PMID
- 10430610
- PMCID
- PMC408418
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Language
- English
- Date published
- 08/01/1999
- 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
- 9984024539702771
Metrics
15 Record Views