Divergent roles for thyroid hormone receptor β isoforms in the endocrine axis and auditory system

E. Dale Abel, Mary Ellen Boers, Carmen Pazos-Moura, Egberto Moura, Helen Kaulbach, Marjorie Zakaria, Bradford Lowell, Sally Radovick, M. Charles Liberman, Fredric Wondisford

Research output: Contribution to journalArticle

Abstract

Thyroid hormone receptors (TRs) modulate various physiological functions in many organ systems. The TRα and TRβ isoforms are products of 2 distinct genes, and the β1 and β2 isoforms are splice variants of the same gene. Whereas TRα1 and TRβ1 are widely expressed, expression of the TRβ2 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 TRβ locus (TRβ-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 TRβ2 isoform to the function of the endocrine and auditory systems in vivo, we have generated mice with targeted disruption of the TRβ2 isoform. TRβ2-null mice have preserved expression of the TRα and TRβ1 isoforms. They develop a similar degree of central resistance to thyroid hormone as TRβ-null mice, indicating the important role of TRβ2 in the regulation of the hypothalamic-pituitary- thyroid axis. Growth hormone gene expression is marginally reduced. In contrast, TRβ2-null mice exhibit no evidence of hearing impairment, indicating that TRβ1 and TRβ2 subserve divergent roles in the regulation of auditory function.

Original languageEnglish (US)
Pages (from-to)291-300
Number of pages10
JournalJournal of Clinical Investigation
Volume104
Issue number3
StatePublished - Aug 1999
Externally publishedYes

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Thyroid Hormone Receptors
Protein Isoforms
Hearing Loss
Thyroid Hormone Resistance Syndrome
Endocrine System
Triiodothyronine
Inner Ear
Thyrotropin
Thyroid Hormones
Growth Hormone
Genes
Retina
Thyroid Gland
Gene Expression
Neurons

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Abel, E. D., Boers, M. E., Pazos-Moura, C., Moura, E., Kaulbach, H., Zakaria, M., ... Wondisford, F. (1999). Divergent roles for thyroid hormone receptor β isoforms in the endocrine axis and auditory system. Journal of Clinical Investigation, 104(3), 291-300.

Divergent roles for thyroid hormone receptor β isoforms in the endocrine axis and auditory system. / Abel, E. Dale; Boers, Mary Ellen; Pazos-Moura, Carmen; Moura, Egberto; Kaulbach, Helen; Zakaria, Marjorie; Lowell, Bradford; Radovick, Sally; Liberman, M. Charles; Wondisford, Fredric.

In: Journal of Clinical Investigation, Vol. 104, No. 3, 08.1999, p. 291-300.

Research output: Contribution to journalArticle

Abel, ED, Boers, ME, Pazos-Moura, C, Moura, E, Kaulbach, H, Zakaria, M, Lowell, B, Radovick, S, Liberman, MC & Wondisford, F 1999, 'Divergent roles for thyroid hormone receptor β isoforms in the endocrine axis and auditory system', Journal of Clinical Investigation, vol. 104, no. 3, pp. 291-300.
Abel ED, Boers ME, Pazos-Moura C, Moura E, Kaulbach H, Zakaria M et al. Divergent roles for thyroid hormone receptor β isoforms in the endocrine axis and auditory system. Journal of Clinical Investigation. 1999 Aug;104(3):291-300.
Abel, E. Dale ; Boers, Mary Ellen ; Pazos-Moura, Carmen ; Moura, Egberto ; Kaulbach, Helen ; Zakaria, Marjorie ; Lowell, Bradford ; Radovick, Sally ; Liberman, M. Charles ; Wondisford, Fredric. / Divergent roles for thyroid hormone receptor β isoforms in the endocrine axis and auditory system. In: Journal of Clinical Investigation. 1999 ; Vol. 104, No. 3. pp. 291-300.
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