epidermal-growth-factor and Goiter

Growing factors influenced on proliferation of follicular cekks of thyroid and probability influence upon a rising of recurrent goitre were presented. Effect of growing factors depending on TSH, specially IGF-1, EGF, FGF and thyroid growth immunoglobulins (TGI) are analysed.

Topics: Epidermal Growth Factor; Fibroblast Growth Factors; Goiter; Growth Substances; Humans; Insulin-Like Growth Factor I; Recurrence; Thyrotropin

Growth regulation of the thyroid has been reinvestigated using an ex vivo system of isolated porcine thyroid follicles. Not only the direct effect of TSH, EGF, IGF I as well as iodine on growth of these follicles has been investigated but also the paracrine communication of these follicles with endothelial cells and fibroblasts. The results of recently published investigations with this culture system are summarized in this article. We could demonstrate that IGF I and EGF have a dose related effect on thyroid cell proliferation, whereas TSH has no effect on thyroid cell growth, if the iodine content of follicles is kept normal. Saturation of thyroid follicles with increasing amounts of iodine (1-40 microM K1) inhibit dose dependent EGF, IGF I or fetal calf serum induced thyroid cell proliferation. Inhibition of iodide organification with PTU or MMI abolish the growth inhibitory effect of iodide indicating that an organified iodinated product is responsible for the growth inhibitory effect of iodide on thyroid cell proliferation. Thyroid follicles secrete a FGF like substance which stimulates the growth of fibroblasts as well as endothelial cells. The secretion of FGF into the culture medium is decreased during TSH stimulation and enhanced during stimulation with EGF. The pretreatment of follicles with iodide abolishes the growth promoting effect of conditioned medium from thyroid follicles on fibroblasts and endothelial cells. We conclude that local growth factors like IGF I and EGF are responsible for thyroid cell proliferation whereas TSH stimulates specific function and hypertrophy of thyroid cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Cell Division; Epidermal Growth Factor; Goiter; Humans; Insulin-Like Growth Factor I; Thyroid Gland; Thyrotropin

Topics: Amino Acid Sequence; Animals; Base Sequence; Chromosome Mapping; Cloning, Molecular; DNA; Epidermal Growth Factor; Gene Expression Regulation; Genetic Markers; Goiter; Humans; Macromolecular Substances; Molecular Weight; Operon; Peptide Fragments; Polymorphism, Genetic; RNA, Messenger; Species Specificity; Thyroglobulin; Thyrotropin; Thyroxine; Transcription, Genetic; Triiodothyronine

Autotaxin (ATX/NPP2) is a tumor cell motility-stimulating factor that displays both a nucleotide pyrophosphatase/phosphodiesterase activity and a recently described lysophospholipase D (lysoPLD) activity. The precise function of ATX in tumor cells and the role of ATX in thyroid carcinoma remains unclear. We have quantified ATX mRNA expression in thyroid carcinoma cell lines and in tissues of patients with thyroid carcinomas. ATX gene activity was significantly higher in undifferentiated anaplastic thyroid carcinoma cell lines (UTC) and tumor tissues as compared to follicular thyroid carcinoma (FTC) cell lines, FTC tissues or goiter tissues that were used as a control. In the thyroid carcinoma cell line 1736, EGF and bFGF stimulated ATX mRNA expression, whereas the cytokines IL-4, IL-1beta and TGF-beta reduced ATX transcriptional levels. FTC-133 cells, stably transfected with an expression vector for ATX, showed a higher lysoPLD activity, a higher proliferation rate and an increased migratory behavior. In addition, ATX also displayed a paracrine stimulatory effect on the motility of different thyroid carcinoma cell lines. Overexpression of ATX in the stably transfected FTC-133 resulted in down-regulation of CD54/ intercellular adhesion molecule-1 (ICAM-1) gene expression and augmented gene activity of the pro-angiogenic chemokine IL-8. We conclude that ATX may be regarded as a new tissue marker for undifferentiated human thyroid carcinoma cells. ATX increases the proliferation and migration of thyroid carcinoma cell lines and may also affect the angiogenic potential of thyroid carcinoma cells. Further studies are needed to provide insight into the role of ATX in the normal and neoplastic thyroid gland.

Topics: Adenocarcinoma, Follicular; Adult; Aged; Aged, 80 and over; Carcinoma; Carcinoma, Papillary; Epidermal Growth Factor; Female; Fibroblast Growth Factor 2; Gene Expression Regulation, Neoplastic; Glucose-6-Phosphate Isomerase; Glycoproteins; Goiter; Humans; Intercellular Adhesion Molecule-1; Interleukin-1; Interleukin-4; Interleukin-8; Male; Middle Aged; Multienzyme Complexes; Phosphodiesterase I; Phosphoric Diester Hydrolases; Pyrophosphatases; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Thyroid Neoplasms; Transfection; Transforming Growth Factor beta; Tumor Cells, Cultured

Thyroid malignancy has been induced by long-term endogenous thyrotropin (TSH) stimulation in experimental animals, leading to local and distant metastasis. It has been postulated that constant and prolonged endogenous TSH stimulation in dyshormonogenetic thyroid tissues could result in thyroid neoplasia. The possible role of growth factors and oncogenes in goitrogenesis and favoring neoplasia has also been mentioned. Overexpression of certain growth factors and/or their receptors, and of oncogenes implicated in growth promotion may play a significant role in the relatively frequent finding of thyroid malignancy in congenital goiters. In this study the expression of epidermal growth factor (EGF), epidermal growth factor receptor (EGF-R), transforming growth factor-beta (TGF-beta), c-myc, and p53 mRNAs was determined in 14 thyroid tissue samples: 6 from patients with thyroid peroxidase (TPO) gene mutations, 4 with thyroglobulin (Tg) gene defects and 4 normal thyroid tissues. EGF mRNA overexpression was seen in 7 of 10 dyshormonogenetic tissues (3.5 to 12.0 arbitrary optical densitometry units [AODU]) and considered significantly higher (p < 0.01) when compared to normal thyroid tissues (0.25 to 0.32 AODU). Moreover, overexpression of EGF-R mRNA was present in 6 of 10 dyshormonogenetic tissues (2.23 to 13.03 AODU) and considered significantly higher (p < 0.01) when compared to normal thyroid tissues (0.42 to 0.65 AODU). There was no difference in c-myc, p53, and TGF-beta mRNAs expression between dyshormonogenetic and normal tissues. The overexpression of EGF and EGF-R mRNAs found in dyshormonogenetic tissues may suggest that this growth factor may play a role in cellular proliferation and contribute to goiter formation.

Topics: Cell Division; Epidermal Growth Factor; ErbB Receptors; Gene Expression; Goiter; Humans; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger; Thyroid Hormones; Transforming Growth Factor beta

While several workers have identified epidermal growth factor (EGF) receptors on human thyroid membranes, very few reports have described EGF effects on intact human thyroid cells in primary culture, and these were short term studies indicating that EGF effects were primarily inhibitory [reduced iodide uptake and thyroglobulin (Tg), T4, and T3 release]. Paradoxically, in vivo EGF stimulates thyroid growth and increases colloid stores. In this study we examined the effects of EGF on cultured thyroid cells in regard to thymidine incorporation, Tg secretion, and cAMP production during a 12-day period. Addition of EGF (0-30 ng/mL) to medium for 6 or 12 days stimulated thymidine incorporation and enhanced Tg synthesis by thyroid cells. However, the profile of Tg release into medium was biphasic. Tg release was inhibited by EGF (0.1-10 ng/mL) during the first 3 days of culture, but the inhibitory effect disappeared by the sixth day, and EGF stimulated Tg release by day 12 and thereafter. EGF enhanced endogenous cAMP levels in thyroid cells, but did not augment TSH-stimulated increases in cAMP production. Our observations of EGF-stimulated growth and inhibited Tg secretion during short term culture are consistent with the findings of earlier studies with nonhuman thyrocytes. However, the later phase of enhanced cAMP levels with stimulation of Tg secretion indicates that EGF may have trophic effects on thyrocytes previously unrecognized because of the short term nature of the studies. These observations suggest an important role for EGF in maintenance of normal thyroid physiology.

Topics: Cells, Cultured; Cyclic AMP; Epidermal Growth Factor; Goiter; Humans; Kinetics; Reference Values; Thyroglobulin; Thyroid Gland; Thyrotropin

Subconfluent human thyroid cells in monolayer, isolated from thyrotoxic tissue or non-toxic goitres obtained at surgery, responded to the addition of epidermal growth factor (EGF) with an increase in cell growth as measured by increased incorporation of [3H]thymidine into trichloroacetic acid-precipitable material. The growth response to EGF was concentration-dependent and the characteristics of the responses were the same using EGF from murine or human sources. With concentrations which stimulated growth, EGF was found to inhibit human thyroid cell function as measured by the release of radioimmunoassayable tri-iodothyronine into the incubation medium. Thyrotrophin (TSH) was also found to stimulate human thyroid cell growth but at concentrations far lower than those used to stimulate thyroid cell function in this system. The effect of EGF on the differentiating action of TSH on human thyroid cells in culture was also investigated; the association of thyroid cells into two-dimensional follicular structures produced by the incubation of thyroid cells at a high cell density with TSH was found to be inhibited by the addition of EGF.

Topics: Cells, Cultured; Epidermal Growth Factor; Goiter; Humans; Hyperthyroidism; Stimulation, Chemical; Thymidine; Thyroid Gland; Thyrotropin; Triiodothyronine