ArticleThe Journal of clinical investigation1999
Novel insight from transgenic mice into thyroid hormone resistance and the regulation of thyrotropin.
Article in The Journal of clinical investigation, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 95 citations in OpenAlex.
- Hypothalamic control of heart rate and body temperature by thyroid hormones.Reviews in endocrine & metabolic disorders · 2026Review
- Emerging roles of brain tanycytes in regulating blood-hypothalamus barrier plasticity and energy homeostasis.Annals of the New York Academy of Sciences · 2023Review
- The Role of Thyroid Hormone in the Regulation of Cerebellar Development.Endocrinology and metabolism (Seoul, Korea) · 2021Article
- The actions of thyroid hormone signaling in the nucleus.Molecular and cellular endocrinology · 2017Review
- Tanycytes control the hormonal output of the hypothalamic-pituitary-thyroid axis.Nature communications · 2017Article
- Role of Thyroid Hormones in Skeletal Development and Bone Maintenance.Endocrine reviews · 2016Review
- Antitumor Responses Stimulated by Dendritic Cells Are Improved by Triiodothyronine Binding to the Thyroid Hormone Receptor β.Cancer research · 2015Article
- Deciphering direct and indirect influence of thyroid hormone with mouse genetics.Molecular endocrinology (Baltimore, Md.) · 2014Review
- The thyroid axis is regulated by NCoR1 via its actions in the pituitary.Endocrinology · 2012Article
- Fundamentally distinct roles of thyroid hormone receptor isoforms in a thyrotroph cell line are due to differential DNA binding.Molecular endocrinology (Baltimore, Md.) · 2012Article
- The adaptor-related protein complex 2, alpha 2 subunit (AP2α2) gene is a peroxisome proliferator-activated receptor cardiac target gene.The protein journal · 2012Article
- Review
- Complete activation of thyroid hormone receptor β by T3 is essential for normal cochlear function and morphology in mice.Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology · 2011Article
- Article
- The p160 coactivator PAS-B motif stabilizes nuclear receptor binding and contributes to isoform-specific regulation by thyroid hormone receptors.The Journal of biological chemistry · 2009Article
- A thyroid hormone receptor mutation that dissociates thyroid hormone regulation of gene expression in vivo.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Another story of mice and men: the types of RTH.Proceedings of the National Academy of Sciences of the United States of America · 2009Article
- Thyroid hormone--sympathetic interaction and adaptive thermogenesis are thyroid hormone receptor isoform--specific.The Journal of clinical investigation · 2001Article
- Critical role for thyroid hormone receptor beta2 in the regulation of paraventricular thyrotropin-releasing hormone neurons.The Journal of clinical investigation · 2001Article
- An unliganded thyroid hormone receptor causes severe neurological dysfunction.Proceedings of the National Academy of Sciences of the United States of America · 2001Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Patients with resistance to thyroid hormone (RTH) exhibit elevated thyroid hormone levels and inappropriate thyrotropin (thyroid-stimulating hormone, or TSH) production. The molecular basis of this disorder resides in the dominant inhibition of endogenous thyroid hormone receptors (TRs) by a mutant receptor. To determine the relative contributions of pituitary versus hypothalamic resistance to the dysregulated production of thyroid hormone in these patients, we developed a transgenic mouse model with pituitary-specific expression of a mutant TR (Delta337T). The equivalent mutation in humans is associated with severe generalized RTH. Transgenic mice developed profound pituitary resistance to thyroid hormone, as demonstrated by markedly elevated baseline and non-triodothyronine (T3)-suppressible serum TSH and pituitary TSH-beta mRNA. Serum thyroxine (T4) levels were only marginally elevated in transgenic mice and thyrotropin-releasing hormone (TRH) gene expression in the paraventricular hypothalamus was downregulated. After TRH administration, T4 concentrations increased markedly in transgenic, but not in wild-type mice. Transgenic mice rendered hypothyroid exhibited a TSH response that was only 30% of the response observed in wild-type animals. These findings indicate that pituitary expression of this mutant TR impairs both T3-mediated suppression and T3-independent activation of TSH production in vivo. The discordance between basal TSH and T4 levels and the reversal with TRH administration demonstrates that resistance at the level of both the thyrotroph and the hypothalamic TRH neurons are required to elevate thyroid hormone levels in patients with RTH.
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