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Making sense with thyroid hormone—the role of T3 in auditory development

Nature Reviews Endocrinology volume 9, pages 296–307 (2013)Cite this article

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Abstract

The senses are our window to the world, our interface with the habitat in which we live in and the basis for our communication with each other. Although sensory systems are not generally viewed as major targets of endocrine regulation, sensory development is profoundly influenced by thyroid hormone (T3) signalling. In this article, we discuss this developmental role of T3 and highlight the auditory system as the best-studied example of the interplay between systemic and local tissue mechanisms by which T3 stimulates the onset of sensory function. Several genes that mediate the action of T3 are known to promote sensory development in mice, including genes that encode T3 receptors and deiodinase enzymes that amplify or deplete levels of T3. We also discuss the current knowledge of sensory defects in human genetic disorders in which T3 signalling is impaired. As sensory input provides the only means of acquiring information from the environment, the stimulation of sensory development is one of the most fundamental functions of T3 signalling.

Key Points

  • An endocrine signal, T3, has considerable control over the development of hearing and other senses in humans and mammalian animal models

  • The exposure of immature sensory tissues to T3 is dynamically regulated by systemic availability of the hormone and by local mechanisms in target tissues

  • T3 is a coordinating signal for the late-stage maturation of the auditory system that promotes the onset of function

  • T3 signalling during the later stages of cochlear development complements other mechanisms of short-range signalling at earlier developmental stages

  • The sensitivity of sensory development to T3 suggests that the senses merit further investigation in human disorders resulting from disrupted T3 signalling

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Figure 1: The mammalian auditory system.
Figure 2: The role of T3 in the development of the mammalian auditory system.
Figure 3: T3 and cochlear development.45,47,129
Figure 4: Biphasic regulation of the T3 signal during cochlear development in mice.

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Acknowledgements

The authors acknowledge the support of the intramural research program at the National Institute of Diabetes and Digestive and Kidney Diseases and at the National Institute on Deafness and other Communication Disorders. The authors thank Dr Francesco Celi for helpful comments.

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Authors and Affiliations

  1. National Institute of Diabetes and Digestive and Kidney Disease, Laboratory of Endocrinology and Receptor Biology, National Institutes of Health, 10 Center Drive, Bethesda, 20892, MD, USA

    Lily Ng & Douglas Forrest

  2. National Institutes of Deafness and Other Communication Disorders, Laboratory of Cochlear Development, National Institutes of Health, 10 Center Drive, Bethesda, 20892, MD, USA

    Matthew W. Kelley

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All authors contributed equally to all aspects of the article.

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Correspondence to Douglas Forrest.

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Ng, L., Kelley, M. & Forrest, D. Making sense with thyroid hormone—the role of T3 in auditory development. Nat Rev Endocrinol 9, 296–307 (2013). https://doi.org/10.1038/nrendo.2013.58

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