ArticleMolecular and cellular biology2005
An unliganded thyroid hormone beta receptor activates the cyclin D1/cyclin-dependent kinase/retinoblastoma/E2F pathway and induces pituitary tumorigenesis.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 105 citations in OpenAlex.
- Molecular biology of pituitary neuroendocrine tumors.Journal of neuro-oncology · 2026Review
- Case Report: Development of a thyrotropinoma in a patient with thyroid hemiagenesis.Frontiers in endocrinology · 2026Article
- The Musashi-1-type 2 deiodinase pathway regulates astrocyte proliferation.The Journal of biological chemistry · 2024Article
- The ageing thyroid: implications for longevity and patient care.Nature reviews. Endocrinology · 2024Review
- The clinical characteristics and gene mutations associated with thyroid hormone resistance syndrome coexisting with pituitary tumors.Frontiers in endocrinology · 2023Review
- Retrospective analysis and literature review of four cases of thyroid hormone resistance syndrome caused byTranslational pediatrics · 2022Article
- Article
- Cell non-autonomous effect of hepatic growth differentiation factor 15 on the thyroid gland.Frontiers in endocrinology · 2022Article
- Thyroid hormone receptor alpha sumoylation modulates white adipose tissue stores.Scientific reports · 2021Article
- Thyroid hormone receptor β sumoylation is required for thyrotropin regulation and thyroid hormone production.JCI insight · 2021Article
- The clinical aspects of pituitary tumour genetics.Endocrine · 2021Review
- Targeting transcriptional regulators for treatment of anaplastic thyroid cancer.Journal of cancer metastasis and treatment · 2021Article
- Nuclear Receptors as Regulators of Pituitary Corticotroph Pro-Opiomelanocortin Transcription.Cells · 2020Review
- Steroid receptor coactivator-3 as a target for anaplastic thyroid cancer.Endocrine-related cancer · 2020Article
- Article
- Mutational Landscape of Resistance to Thyroid Hormone Beta (RTHβ).Molecular diagnosis & therapy · 2019Review
- Analysis of Thyroid Tumorigenesis in Xenograft Mouse Model.Methods in molecular biology (Clifton, N.J.) · 2018Article
- Defective erythropoiesis caused by mutations of the thyroid hormone receptor α gene.PLoS genetics · 2017Article
- Targeting MYC as a Therapeutic Intervention for Anaplastic Thyroid Cancer.The Journal of clinical endocrinology and metabolism · 2017Article
- Loss of tyrosine phosphorylation at Y406 abrogates the tumor suppressor functions of the thyroid hormone receptor β.Molecular carcinogenesis · 2017Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 6 institutions in 3 countries.
Funding
Abstract
Thyroid-stimulating hormone (TSH)-secreting tumors (TSH-omas) are pituitary tumors that constitutively secrete TSH. The molecular genetics underlying this abnormality are not known. We discovered that a knock-in mouse harboring a mutated thyroid hormone receptor (TR) beta (PV; TRbeta(PV/PV) mouse) spontaneously developed TSH-omas. TRbeta(PV/PV) mice lost the negative feedback regulation with highly elevated TSH levels associated with increased thyroid hormone levels (3,3',5-triiodo-l-thyronine [T3]). Remarkably, we found that mice deficient in all TRs (TRalpha1(-/-) TRbeta(-/-)) had similarly increased T3 and TSH levels, but no discernible TSH-omas, indicating that the dysregulation of the pituitary-thyroid axis alone is not sufficient to induce TSH-omas. Comparison of gene expression profiles by cDNA microarrays identified overexpression of cyclin D1 mRNA in TRbeta(PV/PV) but not in TRalpha1(-/-) TRbeta(-/-) mice. Overexpression of cyclin D1 protein led to activation of the cyclin D1/cyclin-dependent kinase/retinoblastoma protein/E2F pathway only in TRbeta(PV/PV) mice. The liganded TRbeta repressed cyclin D1 expression via tethering to the cyclin D1 promoter through binding to the cyclic AMP response element-binding protein. That repression effect was lost in mutant PV, thereby resulting in constitutive activation of cyclin D1 in TRbeta(PV/PV) mice. The present study revealed a novel molecular mechanism by which an unliganded TRbeta mutant acts to contribute to pituitary tumorigenesis in vivo and provided mechanistic insights into the understanding of pathogenesis of TSH-omas in patients.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.