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A protective role for type 3 deiodinase, a thyroid hormone-inactivating enzyme, in cochlear development and auditory
Lily Ng1, Arturo Hernandez, Wenxuan He
1National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Clinical Endocrinology Branch, Bethesda, Maryland 20892-1772, USA.
Endocrinology
|December 20, 2008
Summary
Type 3 deiodinase protects hearing by regulating thyroid hormone levels in the developing cochlea. Its absence causes auditory deficits and accelerated cochlear development.
Area of Science:
- Developmental Biology
- Endocrinology
- Auditory Science
Background:
- Thyroid hormone is crucial for cochlear development and auditory function.
- Type 2 deiodinase amplifies active thyroid hormone (T3) in the cochlea before hearing onset.
- Factors controlling these processes remain poorly understood.
Purpose of the Study:
- To investigate the role of type 3 deiodinase in cochlear development and auditory function.
- To elucidate the interaction between type 3 deiodinase, type 2 deiodinase, and thyroid hormone receptor beta (TRbeta) in the auditory system.
Main Methods:
- Analysis of Dio3 knockout (Dio3-/-) mice to assess cochlear development and auditory function.
- Examination of Dio3 mRNA expression patterns in the immature cochlea.
- Deletion of thyroid hormone receptor beta (TRbeta) in Dio3-/- mice to evaluate its impact on the cochlear phenotype.
Main Results:
- Type 3 deiodinase is expressed in the immature cochlea before type 2 deiodinase.
- Dio3-/- mice exhibit auditory deficits and accelerated cochlear differentiation.
- Deleting TRbeta in Dio3-/- mice reversed the accelerated differentiation to delayed differentiation, supporting a protective role for type 3 deiodinase.
Conclusions:
- Type 3 deiodinase plays a protective role in hearing by preventing premature stimulation of TRbeta.
- The auditory system demonstrates autoregulation of thyroid hormone response via type 2 and type 3 deiodinases.
- These findings enhance understanding of thyroid hormone's role in auditory development and potential therapeutic targets.
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