Hypothyroidism in Thyroid Transcription Factor 1 Haploinsufficiency Is Caused by Reduced Expression of the Thyroid-Stimulating Hormone Receptor
Copyright policy )Hypothyroidism in Thyroid Transcription Factor 1 Haploinsufficiency Is Caused by Reduced Expression of the Thyroid-Stimulating Hormone Receptor
Humans expressing one allele of the thyroid transcription factor 1 (TTF1) gene have neurological symptoms and increased serum TSH with variable degrees of hypothyroidism. Ttf1+/- mice have also poor coordination and increased serum TSH concentration (205 +/- 22 vs. 92 +/- 12 mU/liter; P 0.05). No significant difference between the two genotypes was found for Pax8, sodium iodide symporter, and iodothyronine deiodinase 1. These results show that Ttf1 haploinsufficiency causes a reduction in the expression of TSHr and thyroglobulin, genes with TTF1 binding sites in their promoter regions. The low TSHr is only partially compensated by an increase in TSH secretion because T4 remains mildly reduced. However, administration of a larger amount of TSH obliterates the response differences by saturating a reduced amount of receptor.
- Université Libre de Bruxelles Belgium
- National Cancer Institute United States
- University of Chicago United States
- Erasmus Hospital Belgium
- National Institutes of Health United States
Male, Mice, Knockout, Adolescent, Base Sequence, Thyroid Nuclear Factor 1, Infant, Newborn, Infant, Nuclear Proteins, Receptors, Thyrotropin, Sciences bio-médicales et agricoles, Thyroid Function Tests, Mice, Phenotype, Hypothyroidism, Child, Preschool, Animals, Humans, Female, RNA, Messenger, Child, Gene Deletion
Male, Mice, Knockout, Adolescent, Base Sequence, Thyroid Nuclear Factor 1, Infant, Newborn, Infant, Nuclear Proteins, Receptors, Thyrotropin, Sciences bio-médicales et agricoles, Thyroid Function Tests, Mice, Phenotype, Hypothyroidism, Child, Preschool, Animals, Humans, Female, RNA, Messenger, Child, Gene Deletion
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