Angiogenesis is an important component in the development of thyroid goitre. Vascular endothelial growth factor (VEGF) represents a family of specific endothelial cell mitogens involved in normal angiogenesis and in tumour development. The purpose of this study was to determine the distribution of VEGF in thyroid tissues during goitre formation, and to study the actions of VEGF on the regulation of thymidine incorporation and iodine uptake by thyroid follicular cells. Goitre was induced in adult rats by administration of methimazole together with a low iodine diet. Thyroid from normal or goitrous rats was removed, fixed and sectioned. Immunocytochemistry performed for VEGF using the avidin-biotin system showed that VEGF is present in normal thyroid and is located mainly in the vascular endothelium and interfollicular stromal tissue. After administration of goitrogen for 2 weeks, which caused a two- to threefold increase in thyroid weight, staining of VEGF was less apparent within the interfollicular stroma, but strongly increased throughout the thyroid follicular and endothelial cells. Uptake of [125I] and incorporation of [3H]thymidine by Fisher rat thyroid cells (FRTL-5) were measured after 72 h culture with or without TSH or VEGF, or both. In the absence of TSH, incubation with VEGF caused a significant reduction in [3H]thymidine incorporation, but did not significantly alter [125I] uptake. Incubation with TSH (1 mU/ml) caused a fourfold increase in [3H]thymidine incorporation that was diminished by co-incubation with 10 ng/ml or greater VEGF. Similarly, 10 ng/ml or greater VEGF significantly reduced the ability of TSH to increase [125I] uptake. The antagonistic effects of VEGF on TSH-stimulated [3H]thymidine incorporation or [125I] uptake were significantly reduced in the presence of an anti-VEGF antiserum. A DNA fragment representing mRNA encoding the VEGF receptor, flt-1, was identified in FRTL-5 cells by reverse transcription PCR analysis, and the abundance of this fragment was increased in FRTL-5 cells cultured in the medium containing TSH (1 mU/ml) or fibroblast growth factor (FGF)-2 (25 ng/ml). These results indicated that VEGF and one of its receptors, Flt-1, are present in epithelial cells of the thyroid, and that VEGF could contribute to the regulation of development and function of thyroid epithelial cells.

This article has been cited by other articles:

				A.-C. Gerard, S. Poncin, B. Caetano, P. Sonveaux, J.-N. Audinot, O. Feron, I. M. Colin, and F. Soncin Iodine Deficiency Induces a Thyroid Stimulating Hormone-Independent Early Phase of Microvascular Reshaping in the Thyroid Am. J. Pathol., March 1, 2008; 172(3): 748 - 760. [Abstract] [Full Text] [PDF]

				I. Tamaskar, R. Bukowski, P. Elson, A. G. Ioachimescu, L. Wood, R. Dreicer, T. Mekhail, J. Garcia, and B. I. Rini Thyroid function test abnormalities in patients with metastatic renal cell carcinoma treated with sorafenib Ann. Onc., February 1, 2008; 19(2): 265 - 268. [Abstract] [Full Text] [PDF]

				B. I. Rini, I. Tamaskar, P. Shaheen, R. Salas, J. Garcia, L. Wood, S. Reddy, R. Dreicer, and R. M. Bukowski Hypothyroidism in Patients With Metastatic Renal Cell Carcinoma Treated With Sunitinib J Natl Cancer Inst, January 3, 2007; 99(1): 81 - 83. [Abstract] [Full Text] [PDF]

				D. S. Kim, J. A. Franklyn, K. Boelaert, M. C. Eggo, J. C. Watkinson, and C. J. McCabe Pituitary Tumor Transforming Gene (PTTG) Stimulates Thyroid Cell Proliferation via a Vascular Endothelial Growth Factor/Kinase Insert Domain Receptor/Inhibitor of DNA Binding-3 Autocrine Pathway J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4603 - 4611. [Abstract] [Full Text] [PDF]

				H. E. Turner, A. L. Harris, S. Melmed, and J. A. H. Wass Angiogenesis in Endocrine Tumors Endocr. Rev., October 1, 2003; 24(5): 600 - 632. [Abstract] [Full Text] [PDF]

				V. A. Patel, A. Logan, J. C. Watkinson, S. Uz-Zaman, M. C. Sheppard, J. D. Ramsden, and M. C. Eggo Isolation and characterization of human thyroid endothelial cells Am J Physiol Endocrinol Metab, January 1, 2003; 284(1): E168 - E176. [Abstract] [Full Text] [PDF]

				R. M. Tuttle, M. Fleisher, G. L. Francis, and R. J. Robbins Serum Vascular Endothelial Growth Factor Levels Are Elevated in Metastatic Differentiated Thyroid Cancer but Not Increased by Short-Term TSH Stimulation J. Clin. Endocrinol. Metab., April 1, 2002; 87(4): 1737 - 1742. [Abstract] [Full Text] [PDF]

				A.-C. Gerard, M.-C. Many, C. Daumerie, S. Costagliola, F. Miot, J. J. M. DeVijlder, I. M. Colin, and J.-F. Denef Structural Changes in the Angiofollicular Units between Active and Hypofunctioning Follicles Align with Differences in the Epithelial Expression of Newly Discovered Proteins Involved in Iodine Transport and Organification J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1291 - 1299. [Abstract] [Full Text] [PDF]

				K. R. S. Brown, K. M. England, K. L. Goss, J. M. Snyder, and M. J. Acarregui VEGF induces airway epithelial cell proliferation in human fetal lung in vitro Am J Physiol Lung Cell Mol Physiol, October 1, 2001; 281(4): L1001 - L1010. [Abstract] [Full Text] [PDF]