ArticleMolecular endocrinology (Baltimore, Md.)2008
Gbetagamma dimers released in response to thyrotropin activate phosphoinositide 3-kinase and regulate gene expression in thyroid cells.
Article in Molecular endocrinology (Baltimore, Md.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 64 citations in OpenAlex.
- TSH upregulates CYP4B1 through the PI3K/AKT/CREB pathway to promote cardiac hypertrophy.Journal of endocrinological investigation · 2025Article
- Transcriptomic analysis reveals a critical role for activating GScientific reports · 2024Article
- Defining theThyroid : official journal of the American Thyroid Association · 2024Article
- Review of the PRIODAC project on thyroid protection from radioactive iodine by repeated iodine intake in individuals aged 12.European thyroid journal · 2024Review
- The role of miR-139-5p in radioiodine-resistant thyroid cancer.Journal of endocrinological investigation · 2023Article
- Sox9 is involved in the thyroid differentiation program and is regulated by crosstalk between TSH, TGFβ and thyroid transcription factors.Scientific reports · 2022Article
- Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion.Frontiers in endocrinology · 2022Review
- Obese patients with higher TSH levels had an obvious metabolic improvement after bariatric surgery.Endocrine connections · 2021Article
- Review
- Unraveling the Complex Interplay Between Transcription Factors and Signaling Molecules in Thyroid Differentiation and Function, From Embryos to Adults.Frontiers in endocrinology · 2021Review
- Proteomic Analysis of Iodinated Contrast Agent-Induced Perturbation of Thyroid Iodide Uptake.Journal of clinical medicine · 2020Article
- TSH/IGF-1 Receptor Cross-Talk Rapidly Activates Extracellular Signal-Regulated Kinases in Multiple Cell Types.Endocrinology · 2017Article
- Somatostatin activates Ras and ERK1/2 via a G protein βγ-subunit-initiated pathway in thyroid cells.Molecular and cellular biochemistry · 2016Article
- Graves' Disease Mechanisms: The Role of Stimulating, Blocking, and Cleavage Region TSH Receptor Antibodies.Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme · 2015Review
- Targeting the thyroid-stimulating hormone receptor with small molecule ligands and antibodies.Expert opinion on therapeutic targets · 2015Review
- Thyroid-stimulating hormone decreases HMG-CoA reductase phosphorylation via AMP-activated protein kinase in the liver.Journal of lipid research · 2015Article
- TSH-receptor-expressing fibrocytes and thyroid-associated ophthalmopathy.Nature reviews. Endocrinology · 2015Review
- Molecular mechanisms of 2, 3', 4, 4', 5-pentachlorobiphenyl-induced thyroid dysfunction in FRTL-5 cells.PloS one · 2015Article
- Wnt-independent role of β-catenin in thyroid cell proliferation and differentiation.Molecular endocrinology (Baltimore, Md.) · 2014Article
- Thyrotropin regulates IL-6 expression in CD34+ fibrocytes: clear delineation of its cAMP-independent actions.PloS one · 2013Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Signaling by TSH through its receptor leads to the dissociation of trimeric G proteins into Galpha and Gbetagamma. Galphas activates adenylyl cyclase, which increases cAMP levels that induce several effects in the thyroid cell, including transcription of the sodium-iodide symporter (NIS) gene through a mechanism involving Pax8 binding to the NIS promoter. Much less is known about the function of Gbetagamma in thyroid differentiation, and therefore we studied their role in TSH signaling. Gbetagamma overexpression inhibits NIS promoter activation and reduces NIS protein accumulation in response to TSH and forskolin. Conversely, inhibition of Gbetagamma-dependent pathways increases NIS promoter activity elicited by TSH but does not modify forskolin-induced activation. Gbetagamma dimers are being released from the Gs subfamily of proteins, because cholera toxin mimics the effects elicited by TSH, whereas pertussis toxin has no effect on NIS promoter activity. We also found that TSH stimulates Akt phosphorylation in a phosphoinositide 3-kinase (PI3K)-dependent and cAMP-independent manner. This is mediated by Gbetagamma, because its overexpression or specific sequestration, respectively, increased or reduced phosphorylated Akt levels upon TSH stimulation. Gbetagamma sequestration increases NIS protein levels induced by TSH and Pax8 binding to the NIS promoter, which is also increased by PI3K inhibition. This is, at least in part, caused by Gbetagamma-mediated Pax8 exclusion from the nucleus that is attenuated when PI3K activity is blocked. These data unequivocally demonstrate that Gbetagamma released by TSH action stimulate PI3K, inhibiting NIS gene expression in a cAMP-independent manner due to a decrease in Pax8 binding to the NIS promoter.
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Registered trials
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.