1. Dietary thyroid hormone replacement ameliorates hearing deficits in hypothyroid mice.
- Author
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Karolyi IJ, Dootz GA, Halsey K, Beyer L, Probst FJ, Johnson KR, Parlow AF, Raphael Y, Dolan DF, and Camper SA
- Subjects
- Administration, Oral, Animals, Hearing Disorders blood, Hearing Disorders etiology, Homeodomain Proteins genetics, Hormone Replacement Therapy, Hypothyroidism blood, Hypothyroidism complications, Hypothyroidism genetics, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Mutant Strains, Mice, Transgenic, Models, Biological, Organ of Corti anatomy & histology, Organ of Corti growth & development, Otoacoustic Emissions, Spontaneous genetics, Receptors, Thyrotropin genetics, Thyroxine blood, Transcription Factor Pit-1 genetics, Diet, Hearing Disorders drug therapy, Hypothyroidism drug therapy, Triiodothyronine administration & dosage, Triiodothyronine therapeutic use
- Abstract
Thyroid hormone (TH) insufficiency causes variable hearing impairment and mental deficiency in humans. Rodents lacking TH have congenital hearing deficiency that has been attributed to physiologic, morphologic, and developmental abnormalities of the auditory system. We examined four genetically defined strains of hypothyroid mice for development of hearing and response to TH replacement initiated during late gestation and continued through six weeks of age. Auditory brain stem response studies showed variable hearing impairment in homozygous mutants of each strain at three weeks of age relative to normal littermates. Mutants from three of the strains still had hearing deficiencies at six weeks of age. TH-enriched diet significantly improved hearing in three-week-old mutants of each strain relative to untreated mutants. Differences in the level of hearing impairment between the Prop1df and Pit1dw mutants, which have defects in the same developmental pathway, were determined to be due to genetic background modifier genes. Further physiologic and morphologic studies in the Cgatm1Sac strain indicated that poor hearing was due to cochlear defects. We conclude that TH supplement administered during the critical period of hearing development in mice can prevent deafness associated with congenital hypothyroidism of heterogeneous genetic etiology.
- Published
- 2007
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