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Stimulation by thyroid-stimulating hormone and Grave's immunoglobulin G of vascular endothelial growth factor mRNA expression in human thyroid follicles in vitro and flt mRNA expression in the rat thyroid in vivo.
Open accessAbstract
To elucidate the pathogenesis of thyroid gland hypervascularity in patients with Graves' disease, we studied the expression of mRNAs for vascular endothelial growth factor (VEGF) and its receptor, Flt family, using human thyroid follicles in vitro and thiouracil-fed rats in vivo. Human thyroid follicles, cultured in the absence of endothelial cells, secreted de novo-synthesized thyroid hormone in response to thyroid-stimulating hormone (TSH) and Graves' IgG. The thyroid follicles produced VEGF mRNA but not flt-1 mRNA. The expression of VEGF mRNA was enhanced by insulin, tumor-promoting phorbol ester, calcium ionophore, dibutyryl cAMP, TSH, and Graves' IgG. When rats were fed thiouracil for 4 wk, their serum levels of TSH were increased at day 3. VEGF mRNA was also increased on day 3, accompanied by an increase in flt family (flt-1 and KDR/ flk-1) mRNA expression. These in vitro and in vivo findings suggest that VEGF is produced by thyroid follicles in response to stimulators of TSH receptors, via the protein kinase A and C pathways. VEGF, a secretable angiogenesis factor, subsequently stimulates Flt receptors on endothelial cells in a paracrine manner, leading to their proliferation and producing hypervascularity of the thyroid gland, as seen in patients with Graves' disease.
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“The activity of Ang-1 can enhance VEGF receptor function for vascular development, remodeling, stabilization, and final maturation (85)(86)(87)”
From Adipose tissue remodeling and obesity (2011) · cites this paper as [87]
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Metadata
- Authors
- Sato, K., Yamazaki, K., Shizume, K., Kanaji, Y., Obara, T., Ohsumi, K., Demura, H., Yamaguchi, S., & Shibuya, M.
- Affiliations
- Tokyo Women's Medical University (JP)
- Institute of Medical Science, The University of Tokyo (JP)
- Venue
- Journal of Clinical Investigation
- Published
- 1995-09-01
- Volume
- 96
- Issue
- 3
- Pages
- 1295-1302
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC185751
- OpenAlex
- W2163384356
- Cited by
- 179
- References
- 42
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 3 · 2023: 2 · 2022: 3 · 2021: 1 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 4 · 2015: 7 · 2014: 2 · 2013: 7 · 2012: 2
- FWCI
- 4.75
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Institute of Medical Science, University of Tokyo
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Keywords
- Graves' disease, vascular endothelial growth factor, VEGF mRNA expression, Flt-1, KDR/Flk-1, thyroid follicles, thyroid-stimulating hormone, thyroid hormone secretion, protein kinase A, protein kinase C, angiogenesis, paracrine signaling, thiouracil
- MeSH terms
- Calcimycin, Animals, Cell Division, Cells, Cultured, Bucladesine, Dose-Response Relationship, Drug, Graves Disease, Humans, Immunoglobulin G, Insulin, Kinetics, Lymphokines, Proto-Oncogene Proteins, RNA, Messenger, Tetradecanoylphorbol Acetate, Thiouracil, Thyroid Gland, Thyrotropin, DNA Probes, Gene Expression, Endothelial Growth Factors, Culture Media, Conditioned, Receptors, Growth Factor, Receptor Protein-Tyrosine Kinases, Vascular Endothelial Growth Factor Receptor-1, Vascular Endothelial Growth Factors, Vascular Endothelial Growth Factor A, Rats
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