Divergent roles for thyroid hormone receptor beta isoforms in the endocrine axis and auditory system.
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.
Pubmed ID: 10430610
- Abel ED
- Boers ME
- Pazos-Moura C
- Moura E
- Kaulbach H
- Zakaria M
- Lowell B
- Radovick S
- Liberman MC
- Wondisford F
The Journal of clinical investigation
August 17, 1999
- Agency: NIDDK NIH HHS, Id: DK-02485
- Agency: NIDDK NIH HHS, Id: DK-49126
- Agency: NIDDK NIH HHS, Id: DK-50564
- Auditory Pathways
- Crosses, Genetic
- Evoked Potentials, Auditory, Brain Stem
- Gene Expression Regulation
- Growth Hormone
- Mice, Inbred C57BL
- Mice, Knockout
- Protein Isoforms
- Receptors, Thyroid Hormone
- Thyroid hormone resistance, autosomal recessive is related to genes THRB, ERBA2, THR1, PRTH which are autosomal recessive according to the OMIM database.
- Thyroid hormone resistance is related to genes THRB, ERBA2, THR1, PRTH which are autosomal dominant according to the OMIM database.
- Thyroid hormone resistance, selective pituitary is related to genes THRB, ERBA2, THR1, PRTH which are autosomal dominant according to the OMIM database.