title: Thyroid hormone receptors control developmental maturation of the middle ear and the size of the ossicular bones.
abstract: Thyroid hormone is critical for auditory development and has well-known actions in the inner ear. However, less is known of thyroid hormone functions in the middle ear, which contains the ossicles (malleus, incus, stapes) that relay mechanical sound vibrations from the outer ear to the inner ear. During the later stages of middle ear development, prior to the onset of hearing, middle ear cavitation occurs, involving clearance of mesenchyme from the middle ear cavity while the immature cartilaginous ossicles attain appropriate size and ossify. Using in situ hybridization, we detected expression of Thra and Thrb genes encoding thyroid hormone receptors α1 and β (TRα1 and TRβ, respectively) in the immature ossicles, surrounding mesenchyme and tympanic membrane in the mouse. Thra(+/PV) mice that express a dominant-negative TRα1 protein exhibited deafness with elevated auditory thresholds and a range of middle ear abnormalities including chronic persistence of mesenchyme in the middle ear into adulthood, markedly enlarged ossicles, and delayed ossification of the ossicles. Congenitally hypothyroid Tshr(-/-) mice and TR-deficient Thra1(-/-);Thrb(-/-) mice displayed similar abnormalities. These findings demonstrate that middle ear maturation is TR dependent and suggest that the middle ear is a sensitive target for thyroid hormone in development.
authors.affiliation: Laboratory of Endocrinology and Receptor Biology, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 10 Center Drive, Bethesda, Maryland 20892-1772, USA.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Cordas
authors.forename: Lily
authors.initials: L
authors.lastname: Ng
authors.forename: Arturo
authors.initials: A
authors.lastname: Hernandez
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kaneshige
authors.forename: Sheue-Yann
authors.initials: SY
authors.lastname: Cheng
authors.forename: Douglas
authors.initials: D
authors.lastname: Forrest
mesh_terms: D000818:Animals; D004432:Ear, Middle / Q000378:metabolism*; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006309:Hearing; D017403:In Situ Hybridization; D007188:Incus / Q000196:embryology; D008297:Male; D008307:Malleus / Q000196:embryology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D011988:Receptors, Thyroid Hormone / Q000502:physiology*; D011989:Receptors, Thyrotropin / Q000502:physiology; D013199:Stapes / Q000196:embryology; D037021:Thyroid Hormone Receptors alpha / Q000502:physiology; D037042:Thyroid Hormone Receptors beta / Q000502:physiology
chemical_list: D011988:Receptors, Thyroid Hormone; D011989:Receptors, Thyrotropin; D037021:Thyroid Hormone Receptors alpha; D037042:Thyroid Hormone Receptors beta