A Protective Role for Type 3 Deiodinase, a Thyroid Hormone-inactivating Enzyme, in Cochlear Development and Auditory Function

Overview

Journal Endocrinology

Publisher Oxford University Press

Specialty Endocrinology

Date 2008 Dec 20

PMID 19095741

Citations 83

Authors

Lily Ng

Arturo Hernandez

Wenxuan He

Tianying Ren

Maya Srinivas

Michelle Ma

Valerie A Galton

Donald L St Germain

Douglas Forrest

Affiliations

Soon will be listed here.

Abstract

Thyroid hormone is necessary for cochlear development and auditory function, but the factors that control these processes are poorly understood. Previous evidence indicated that in mice, the serum supply of thyroid hormone is augmented within the cochlea itself by type 2 deiodinase, which amplifies the level of T(3), the active form of thyroid hormone, before the onset of hearing. We now report that type 3 deiodinase, a thyroid hormone-inactivating enzyme encoded by Dio3, is expressed in the immature cochlea before type 2 deiodinase. Dio3-/- mice display auditory deficits and accelerated cochlear differentiation, contrasting with the retardation caused by deletion of type 2 deiodinase. The Dio3 mRNA expression pattern in the greater epithelial ridge, stria vascularis, and spiral ganglion partly overlaps with that of thyroid hormone receptor beta (TRbeta), the T(3) receptor that is primarily responsible for auditory development. The proposal that type 3 deiodinase prevents premature stimulation of TRbeta was supported by deleting TRbeta, which converted the Dio3-/- cochlear phenotype from one of accelerated to one of delayed differentiation. The results indicate a protective role for type 3 deiodinase in hearing. The auditory system illustrates the considerable extent to which tissues can autoregulate their developmental response to thyroid hormone through both type 2 and 3 deiodinases.

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