This Article Full Text Full Text (PDF) Supplemental Data A correction has been published Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ng, L. Articles by Forrest, D. Search for Related Content PubMed PubMed Citation Articles by Ng, L. Articles by Forrest, D.

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

National Institutes of Health (L.N., M.M., D.F.), National Institute of Diabetes and Digestive and Kidney Diseases, Clinical Endocrinology Branch, Bethesda, Maryland 20892-1772; Departments of Medicine (A.H., V.A.G., D.L.S.) and Physiology (D.L.S.), Dartmouth Medical School, Lebanon, New Hampshire 03756; Oregon Health & Science University (W.H., T.R.), Department of Otolaryngology, Head and Neck Surgery, Portland, Oregon 97239-3098; and Department of Human Genetics (M.S.), Mount Sinai School of Medicine, New York, New York 10029

Address all correspondence and requests for reprints to: Douglas Forrest, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Clinical Endocrinology Branch, 10 Center Drive, Bethesda, Maryland 20892-1772. E-mail: forrestd{at}niddk.nih.gov.

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 T₃, 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 β (TRβ), the T₃ receptor that is primarily responsible for auditory development. The proposal that type 3 deiodinase prevents premature stimulation of TRβ was supported by deleting TRβ, 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.

This article has been cited by other articles:

				G. Aerts, R. Arrojo e Drigo, S. L. J. Van Herck, E. Sammels, D. Mirebeau-Prunier, B. Gereben, A. Zeold, J. W. Harney, S. A. Huang, M. A. Mulcahey, et al. Knockdown of the Type 3 Iodothyronine Deiodinase (D3) Interacting Protein Peroxiredoxin 3 Decreases D3-Mediated Deiodination in Intact Cells Endocrinology, November 1, 2009; 150(11): 5171 - 5180. [Abstract] [Full Text] [PDF]

				P. Wangemann, H.-M. Kim, S. Billings, K. Nakaya, X. Li, R. Singh, D. S. Sharlin, D. Forrest, D. C. Marcus, and P. Fong Developmental delays consistent with cochlear hypothyroidism contribute to failure to develop hearing in mice lacking Slc26a4/pendrin expression Am J Physiol Renal Physiol, November 1, 2009; 297(5): F1435 - F1447. [Abstract] [Full Text] [PDF]