transforming-growth-factor-beta and Thyroid-Diseases

Transforming growth factor beta (TGF-β), as a master regulator of immune response, is deeply implicated in the complex pathophysiology and development of autoimmune thyroid diseases. Based on the close interplay between thyroid autoimmunity and TGF-β, scientific interest was shifted to the understanding of the possible role of this molecule regarding the diagnosis, prognosis, and therapy of these diseases. The main aim of this review is to present research data about possible treatment options based on the role of TGF-β in thyroid autoimmunity. Suggested TGF-β-mediated therapeutic strategies regarding autoimmune thyroid diseases include either the enhancement of its immunosuppressive role or inhibition of its facilitatory role in thyroid autoimmunity. For example, the application of hr-TGF-β can be used to bolster the inhibitory role of TGF-β regarding the development of thyroid diseases, whereas anti-TGF-β antibodies and similar molecules could impede its immune-promoting effects by blocking different levels of TGF-β biosynthesis and activation pathways. In conclusion, TGF-β could evolve to a promising, novel therapeutic tool for thyroid autoimmunity.

Topics: Autoimmunity; Humans; Immunosuppressive Agents; Thyroid Diseases; Transforming Growth Factor beta

To study transforming growth factor-beta1 (TGF-beta1) plasma concentrations in elderly patients with nonthyroidal illnesses (NTI).. Case-control study.. We measured plasma concentrations of tri-iodothyronine (T3), reverse T3 (rT3), thyroxine (T4), free T3 (fT3) and free T4 (fT4) estimates, TSH, and TGF-beta1 in 48 elderly NTI patients consecutively admitted in our Division of Internal Medicine and Metabolic Diseases, and in 11 healthy age- and sex-matched controls.. The data on thyroid hormones enabled us to identify three groups: Group A, subjects (8 patients) with T3 and fT3 levels comparable to those in controls: Group B, subjects (30 patients) with T3 and fT3 levels lower than controls but rT3 levels comparable to those of controls; Group C, subjects (10 patients) with T3 and fT3 levels lower than those of controls and higher rT3 levels. The patients of Group C showed higher plasma levels of TGF-beta1 compared with controls. Moreover, we found a positive correlation between TGF-beta1 and rT3 (rs = 0.38, P < 0.01) in the whole group of NTI patients.. Our data seem to confirm the hypothesis that TGF-beta1 could play a role in the pathogenesis of some modifications of thyroid function observed in patients with nonthyroidal illnesses.

Topics: Aged; Case-Control Studies; Female; Humans; Male; Osmolar Concentration; Reference Values; Thyroid Diseases; Transforming Growth Factor beta; Triiodothyronine; Triiodothyronine, Reverse

Measurable endothelin (ET) was found in serum-free medium of cultured primary thyroid cells derived from human thyroid tissues after 3 days incubation at levels ranging from undetectable to 35 fmol/100,000 cells. Out of 12 thyroid glands studied, 2 responded to transforming growth factor-beta (TGF-beta) treatment with increased ET secretion into medium. Detailed study of cells derived from one of these thyroids showed TGF-beta at 1 ng/ml stimulated ET secretion from 13.7 to 33.3 fmol/100,000 cells after 3 days incubation. Although TSH alone did not significantly modulate ET release into medium, TSH enhanced the stimulatory effect of TGF-beta. A combination of TSH at 1 mU/ml and TGF-beta at 1 ng/ml stimulated ET secretion to 63.8 fmol/100,000 cells after 3 days incubation. Immunostaining studies demonstrated the presence of intracellular immunoreactive ET, largely localized in perinuclear regions, which was greatly stimulated by TSH but not by TGF-beta. These observations suggest that TSH may stimulate only ET synthesis, whereas TGF-beta may stimulate both synthesis and secretion. Binding of [125I]ET-1 to receptor on thyroid cells was dose-dependently stimulated by TGF-beta (0-10 ng/ml) pretreatment for 3 days. Scatchard analysis of competitive binding data from TGF-beta (1 ng/ml)-treated cells indicated that increased binding was the result of increased receptor number and not increased receptor affinity. TSH (0-10 mU/ml), though not as potent as TGF-beta, also dose-dependently stimulated ET binding. Treatment of thyrocytes with 1 mU/ml TSH for 3 days did not significantly affect ET receptor number or binding affinity. These results illuminate aspects of a possible autocrine regulation of ET in the thyroid gland.

Topics: Adenoma; Cells, Cultured; Endothelins; Endothelium, Vascular; Goiter; Goiter, Nodular; Graves Disease; Humans; Iodine Radioisotopes; Kinetics; Receptors, Endothelin; Reference Values; Thyroglobulin; Thyroid Diseases; Thyroid Gland; Thyroid Neoplasms; Thyrotropin; Transforming Growth Factor beta