ArticleProceedings of the National Academy of Sciences of the United States of America1996
The human thyrotropin receptor: a heptahelical receptor capable of stimulating members of all four G protein families.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers.
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Who cites it
86 citing papers in PubMed, 316 citations in OpenAlex.
- Substrate for Thyroid Hormone Synthesis: Biochemistry, Evolution, and Physiology.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Thyroid autoimmunity, thyroid function, and endometriosis: reproductive immune-endocrine crosstalk and causal uncertainty.Frontiers in medicine · 2026Review
- TSH upregulates CYP4B1 through the PI3K/AKT/CREB pathway to promote cardiac hypertrophy.Journal of endocrinological investigation · 2025Article
- Contract to kill: GNAS mutation.Molecular cancer · 2025Review
- G-protein coupled receptors synergy in bone health: new avenues for osteoporosis detection andFrontiers in endocrinology · 2025Review
- Severe Phenotype of De Novo TSHR Activating Pathogenic Variants.Case reports in endocrinology · 2025Article
- Melanocortin-4 Receptor PLC Activation Is Modulated by an Interaction with the Monocarboxylate Transporter 8.International journal of molecular sciences · 2024Article
- Mechanisms of thyrotropin receptor-mediated phenotype variability deciphered by gene mutations and M453T-knockin model.JCI insight · 2024Article
- Pathogenesis of cancers derived from thyroid follicular cells.Nature reviews. Cancer · 2023Review
- Article
- Inhibition of TSH/IGF-1 Receptor Crosstalk by Teprotumumab as a Treatment Modality of Thyroid Eye Disease.The Journal of clinical endocrinology and metabolism · 2022Article
- TSH stimulation of human thyroglobulin and thyroid peroxidase gene transcription is partially dependent on internalization.Cellular signalling · 2022Article
- Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion.Frontiers in endocrinology · 2022Review
- Graves' Autoantibodies Exhibit Different Stimulating Activities in Cultures of Thyrocytes and Orbital Fibroblasts Not Reflected by Clinical Assays.Thyroid : official journal of the American Thyroid Association · 2022Article
- Fusion with Promiscuous GαInternational journal of molecular sciences · 2021Article
- Expression and Role of Thyrotropin Receptors in Proopiomelanocortin-Producing Pituitary Cells.Thyroid : official journal of the American Thyroid Association · 2021Article
- Crosstalk Between Abnormal TSHR Signaling Activation and PTEN/PI3K in the Dedifferentiation of Thyroid Cancer Cells.Frontiers in oncology · 2021Article
- Orbital Signaling in Graves' Orbitopathy.Frontiers in endocrinology · 2021Review
- Biased signaling in naturally occurring mutations of G protein-coupled receptors associated with diverse human diseases.Biochimica et biophysica acta. Molecular basis of disease · 2021Review
- Modulating TSH Receptor Signaling for Therapeutic Benefit.European thyroid journal · 2020Article
26 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Thyrotropin is the primary hormone that, via one heptahelical receptor, regulates thyroid cell functions such as secretion, specific gene expression, and growth. In human thyroid, thyrotropin receptor activation leads to stimulation of the adenylyl cyclase and phospholipase C cascades. However, the G proteins involved in thyrotropin receptor action have been only partially defined. In membranes of human thyroid gland, we immunologically identified alpha subunits of the G proteins Gs short, Gs long, Gi1, Gi2, Gi3, G(o) (Go2 and another form of Go, presumably Go1), Gq, G11, G12, and G13. Activation of the thyrotropin (TSH) receptor by bovine TSH led to increased incorporation of the photoreactive GTP analogue [alpha-32P]GTP azidoanilide into immunoprecipitated alpha subunits of all G proteins detected in thyroid membranes. This effect was receptor-dependent and not due to direct G protein stimulation because it was mimicked by TSH receptor-stimulating antibodies of patients suffering from Grave disease and was abolished by a receptor-blocking antiserum from a patient with autoimmune hypothyroidism. The TSH-induced activation of individual G proteins occurred with EC50 values of 5-50 milliunits/ml, indicating that the activated TSH receptor coupled with similar potency to different G proteins. When human thyroid slices were pretreated with pertussis toxin, the TSH receptor-mediated accumulation of cAMP increased by approximately 35% with TSH at 1 milliunits/ml, indicating that the TSH receptor coupled to Gs and G(i). Taken together, these findings show that, at least in human thyroid membranes, in which the protein is expressed at its physiological levels, the TSH receptor resembles a naturally occurring example of a general G protein-activating receptor.
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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.