Role of Transforming Growth Factor Beta in the Regulation of Thyroid Function and Growth
- 1 August 2009
- journal article
- review article
- Published by Mary Ann Liebert Inc in Thyroid®
- Vol. 19 (8), 881-892
- https://doi.org/10.1089/thy.2007.0303
Abstract
Transforming growth factor beta (TGF-β) exists in nature as three isoforms. They exert their effects by binding to a type II receptor located at the cell membrane. The TGF-β-type II receptor complex then recruits type I receptor, and this new complex stimulates the phosphorylation of Smads 2 and 3, which are subsequently transferred to the nucleus, where they regulate gene transcription. The thyroid gland expresses the TGF-β1 gene mRNA and synthesizes the protein, which under physiologic conditions regulates thyroid growth and function. Different studies have demonstrated that TGF-β1 inhibits cell proliferation and a number of functional parameters. These include cyclic adenosine monophosphate (AMP) formation, iodine uptake and organification, hormone secretion, and the expression of thyroglobulin, thyroid peroxidase, and Na+/I− symporter. The expression of the TGF-β1 gene and protein may be stimulated by iodine under normal conditions. Since TGF-β1 mimics some of the inhibitory actions of iodine, its participation in thyroid autoregulation has been proposed; however, this concept is still debated. In thyroid tumors, the inhibitory action of TGF-β1 on cell proliferation is progressively lost as the tumor becomes more undifferentiated. The alterations in the signaling pathway of TGF-β1 are not the same in tumors from different species. Even within the same species, such as the pig thyroid, the results may be different depending on whether monolayers or follicular suspensions are employed. The data suggest that it is not entirely possible to apply the results obtained in animal studies to normal or pathological human thyroid tissue. More studies are required to provide the information needed to develop treatments, based on targeting the signaling pathway of TGF-β1, for undifferentiated thyroid cancer and other thyroid diseases.This publication has 91 references indexed in Scilit:
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