Thyrocyte-specific Gq/G11 deficiency impairs thyroid function and prevents goiter development
Open accessAbstract
The function of the adult thyroid is regulated by thyroid-stimulating hormone (TSH), which acts through a G protein-coupled receptor. Overactivation of the TSH receptor results in hyperthyroidism and goiter. The Gs-mediated stimulation of adenylyl cyclase-dependent cAMP formation has been regarded as the principal intracellular signaling mechanism mediating the action of TSH. Here we show that the Gq/G11-mediated signaling pathway plays an unexpected and essential role in the regulation of thyroid function. Mice lacking the alpha subunits of Gq and G11 specifically in thyroid epithelial cells showed severely reduced iodine organification and thyroid hormone secretion in response to TSH, and many developed hypothyroidism within months after birth. In addition, thyrocyte-specific Galphaq/Galpha11-deficient mice lacked the normal proliferative thyroid response to TSH or goitrogenic diet, indicating an essential role of this pathway in the adaptive growth of the thyroid gland. Our data suggest that Gq/G11 and their downstream effectors are promising targets to interfere with increased thyroid function and growth.
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Iodine organification and TH secretion in response to TSH are severely reduced in thyrocyte-specific Gαq/11-deficient mice which often develop hypothyroidism after birth.
“Iodine organification and TH secretion in response to TSH are severely reduced in thyrocyte-specific Gαq/11-deficient mice which often develop hypothyroidism after birth (131).”
From Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion (2022) · cites this paper as [131]
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Phosphodiesterase 8B Gene Variants Are Associated with Serum TSH Levels and Thyroid Function
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Intrathyroidal feedforward and feedback network regulating thyroid hormone synthesis and secretion
Jing, L., & Zhang, Q. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.992883 · Cited by 61 · see citing works
- Authors
- Kero, J., Ahmed, K., Wettschureck, N., Tunaru, S., Wintermantel, T., Greiner, E., Schütz, G., & Offermanns, S.
- Affiliations
- Heidelberg University (DE)
- German Cancer Research Center (DE)
- Corresponding author
- Offermanns, Stefan
- Venue
- Journal of Clinical Investigation
- Published
- 2007-09-04
- Volume
- 117
- Issue
- 9
- Pages
- 2399-2407
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC1937498
- OpenAlex
- W2165806416
- Cited by
- 124
- References
- 1
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 7 · 2023: 1 · 2022: 5 · 2021: 4 · 2020: 12 · 2019: 6 · 2018: 9 · 2017: 5 · 2016: 2 · 2015: 9 · 2014: 7 · 2013: 8 · 2012: 4
- FWCI
- 6.04
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Universität Heidelberg
- National Institute of Diabetes and Digestive and Kidney Diseases
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- G protein-coupled receptors, thyroid-stimulating hormone, TSH receptor, thyroid follicular cells, goiter, hypothyroidism, thyroid hormone secretion, iodine organification, thyroid growth, Gαq, Gα11, cAMP signaling
- MeSH terms
- Animals, Cells, Cultured, Goiter, Organ Specificity, Thyroid Gland, Thyrotropin, Mice, Knockout, GTP-Binding Protein alpha Subunits, Gq-G11, Mice
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