scholarly journals FOXO1 Controls Thyroid Cell Proliferation in Response to TSH and IGF-I and Is Involved in Thyroid Tumorigenesis

2013 ◽  
Vol 27 (1) ◽  
pp. 50-62 ◽  
Author(s):  
Miguel A. Zaballos ◽  
Pilar Santisteban
Keyword(s):  
Cell Proliferation ◽  
Tumor Cells ◽  
Thyroid Tumor ◽  
Human Thyroid ◽  
Thyroid Cell ◽  
Dependent Manner ◽  
Thyroid Cells ◽  
Differentiated Cells ◽  
Igf I ◽  
Rat Thyroid

TSH and insulin/IGF-I synergistically induce the proliferation of thyroid cells mainly through the cAMP and phosphatidylinositol 3-kinase (PI3K) pathways. However, the events involved in this cooperative induction remain unknown, and molecules that are potentially controlled by both TSH and IGF-I are interesting candidates as integrators of both stimuli. The finding that the PI3K pathway is frequently activated in thyroid malignancies has attracted attention to this pathway in the thyroid field. One of the targets of PI3K is Forkhead box O (FoxO)-1, a widely expressed transcription factor involved in a variety of cellular processes such as differentiation, proliferation, and apoptosis. Here we show that FoxO1 is highly expressed in differentiated rat thyroid cells and human thyroid tissue compared with human thyroid tumor-derived cells and surgically removed thyroid tumors, in which its expression is reduced. In differentiated cells, TSH/cAMP treatment decreases FoxO1 mRNA and protein levels through proteasome activation, whereas both TSH and IGF-I control FoxO1 localization by promoting a rapid exclusion from the nucleus in an Akt-dependent manner. FoxO1 can control p27KIP1 expression in differentiated and tumor cells of the thyroid. Furthermore, FoxO1 reexpression in tumor cells promotes a decrease in their proliferation rate, whereas FoxO1 interference in differentiated cells increases their proliferation. These data point to an important role of FoxO1 in mediating the effects of TSH and IGF-I on thyroid cell proliferation and provide a link between loss of FoxO1 expression and the uncontrolled proliferation of thyroid tumor cells.

Regulation of amino acid transport in rat and human thyroid cells

1989 ◽  
Vol 121 (6) ◽  
pp. 759-766
Author(s):  
C. M. Rotella ◽  
F. Piani ◽  
U. Frediani ◽  
R. Toccafondi
Keyword(s):  
Amino Acid ◽  
Cell Cultures ◽  
Amino Acid Transport ◽  
Human Thyroid ◽  
Thyroid Cell ◽  
Acid Transport ◽  
Thyroid Cells ◽  
Igf I ◽  
Rat Thyroid ◽  
Human Thyroid Cell

Abstract. To clarify the role of insulin, IGF-I and TSH in thyroid cell regulation, their effects on amino acid transport were studied separately. These effects were noted and compared using both the Wistar rat thyroid cell line and human thyroid cell cultures. Insulin, IGF-I and TSH were able independently to induce the radiolabelled α-aminoisobutyric acid transport within the rat thyroid cells: TSH stimulated the amino acid transport in rat thyroid cells in a dose-dependent way from 1 pmol/l to 10 nmol/l. Similarly, insulin increased amino acid transport significantly from 0.17 nmol/1 up to 0.17 μmol/l and IGF-I from 0.13 pmol/l up to 0.13 μmol/l. The combined effects of insulin and TSH on amino acid transport were equal to the theoretical sum of the activities, whereas those of IGF-I and TSH were greater than the theoretical one. When human thyroid cell cultures were used, a significant increase of labelled amino acid transport was induced by TSH, i.e. from 0.1 pmol/l to 10 pmol/l; IGF-I stimulated amino acid transport in a range from 0.13 pmol/l to 13 pmol/l, under the same conditions. Conversely, only large doses of insulin, i.e. 1.7 nmol/l, were able weakly to stimulate amino acid transport. When submaximal TSH and IGF-I doses were co-incubated in human thyroid cells, an additive effect on amino acid transport was observed.

scholarly journals Trace Amine-Associated Receptor 1 Trafficking to Cilia of Thyroid Epithelial Cells

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1518
Author(s):  
Maria Qatato ◽  
Vaishnavi Venugopalan ◽  
Alaa Al-Hashimi ◽  
Maren Rehders ◽  
Aaron D. Valentine ◽  
...  
Keyword(s):  
Cell Surface ◽  
Cell Lines ◽  
Human Thyroid ◽  
Apical Plasma Membrane ◽  
Thyroid Cell ◽  
Thyroid Cells ◽  
Trace Amine ◽  
Rat Thyroid

Trace amine-associated receptor 1 (rodent Taar1/human TAAR1) is a G protein-coupled receptor that is mainly recognized for its functions in neuromodulation. Previous in vitro studies suggested that Taar1 may signal from intracellular compartments. However, we have shown Taar1 to localize apically and on ciliary extensions in rodent thyrocytes, suggesting that at least in the thyroid, Taar1 may signal from the cilia at the apical plasma membrane domain of thyrocytes in situ, where it is exposed to the content of the follicle lumen containing putative Taar1 ligands. This study was designed to explore mouse Taar1 (mTaar1) trafficking, heterologously expressed in human and rat thyroid cell lines in order to establish an in vitro system in which Taar1 signaling from the cell surface can be studied in future. The results showed that chimeric mTaar1-EGFP traffics to the apical cell surface and localizes particularly to spherical structures of polarized thyroid cells, procilia, and primary cilia upon serum-starvation. Moreover, mTaar1-EGFP appears to form high molecular mass forms, possibly homodimers and tetramers, in stably expressing human thyroid cell lines. However, only monomeric mTaar1-EGFP was cell surface biotinylated in polarized human thyrocytes. In polarized rat thyrocytes, mTaar1-EGFP is retained in the endoplasmic reticulum, while cilia were reached by mTaar1-EGFP transiently co-expressed in combination with an HA-tagged construct of the related mTaar5. We conclude that Taar1 trafficking to cilia depends on their integrity. The results further suggest that an in vitro cell model was established that recapitulates Taar1 trafficking in thyrocytes in situ, in principle, and will enable studying Taar1 signaling in future, thus extending our general understanding of its potential significance for thyroid autoregulation.

scholarly journals Acrylamide does not induce tumorigenesis or major defects in mice in vivo

2008 ◽  
Vol 198 (2) ◽  
pp. 301-307 ◽  
Author(s):  
Ling Jin ◽  
Vanessa Chico-Galdo ◽  
Claude Massart ◽  
Christine Gervy ◽  
Viviane De Maertelaere ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Chronic Administration ◽  
Serum Levels ◽  
Human Thyroid ◽  
Thyroid Cell ◽  
Thyroid Cells ◽  
Hormone Synthesis ◽  
Rat Thyroid

Chronic administration of acrylamide has been shown to induce thyroid tumors in rat. In vitro acrylamide also causes DNA damage, as demonstrated by the comet assay, in various types of cells including human thyroid cells and lymphocytes, as well as rat thyroid cell lines. In this work, mice were administered acrylamide in their drinking water in doses comparable with those used in rats, i.e., around 3–4 mg/kg per day for mice treated 2, 6, and 8 months. Some of the mice were also treated with thyroxine (T4) to depress the activity of the thyroid. Others were treated with methimazole that inhibits thyroid hormone synthesis and consequently secretion and thus induces TSH secretion and thyroid activation. These moderate treatments were shown to have their known effect on the thyroid (e.g. thyroid hormone and thyrotropin serum levels, thyroid gland morphology…). Besides, T4 induced an important polydipsia and degenerative hypertrophy of adrenal medulla. Acrylamide exerted various discrete effects and at high doses caused peripheral neuropathy, as demonstrated by hind-leg paralysis. However, it did not induce thyroid tumorigenesis. These results show that the thyroid tumorigenic effects of acrylamide are not observed in another rodent species, the mouse, and suggest the necessity of an epidemiological study in human to conclude on a public health policy.

Differential effects of interleukin 1α and 1β on cultured human and rat thyroid epithelial cells

1990 ◽  
Vol 122 (4) ◽  
pp. 520-526 ◽  
Author(s):  
Å. Krogh Rasmussen ◽  
L. Kayser ◽  
K. Bech ◽  
U. Feldt-Rasmussen ◽  
H. Perrild ◽  
...  
Keyword(s):  
Cell Line ◽  
Interleukin 1 ◽  
Cell System ◽  
Human Thyroid ◽  
Thyroid Cell ◽  
Camp Production ◽  
Thyroid Cells ◽  
Thyroid Cell Line ◽  
Interleukin 1Α ◽  
Rat Thyroid

Abstract The effects of human recombinant interleukin 1α (20 pg/1-2 μg/l) and 1β (200 pg/1-20 μg/l) on two systems of thyroid cells have been compared. The thyroglobulin and cAMP secretion and the DNA content of human thyroid cells cultured in monolayer and of continuously grown rat thyroid cells, Fischer rat thyroid cell line have been studied. The growth of the rat thyroid cell line was inhibited by interleukin 1β (20 ng/1-20 μg/l), but not by interleukin 1α. None of the cytokines changed the cAMP production of the rat thyroid cells. In contrast, both cAMP production and thyroglobulin secretion were inhibited dose-dependently by the cytokines in human thyroid cells in secondary cultures. These results caution the interpretation and extrapolation of changes induced by interleukin 1 from one cell system to the other.

A comparison of the bioactivity of human and bovine thyrotrophin preparations, as determined by intracellular cyclic AMP responses of cultured FRTL-5 cells and human thyroid cell monolayers

1984 ◽  
Vol 106 (4) ◽  
pp. 482-489 ◽  
Author(s):  
S. P. Bidey ◽  
K. Ryder ◽  
R. Gaines-Das ◽  
N.J. Marshall ◽  
R. P. Ekins
Keyword(s):  
Cyclic Amp ◽  
Human Thyroid ◽  
Thyroid Cell ◽  
Response Curves ◽  
Thyroid Cells ◽  
Response Parameter ◽  
Reference Preparation ◽  
Single Cell Type ◽  
Rat Thyroid ◽  
Bovine Tsh

Abstract. A clonal strain of thyrotrophin (TSH)-dependent rat thyroid cells (FRTL-5) has been used to evaluate the biological activity of reference preparations of both human and bovine TSH. Using the accumulation of intracellular cyclic AMP as a response parameter, the widely used bovine TSH preparation. Armour 'Thytropar', was calibrated against the First International Standard of Thyrotrophin (pituitary TSH), bovine, for immunoassay. Log dose – log response curves were parallel, and a relative potency of 2.4 IU/unit of 'Thytropar' was obtained. Subcultures of FRTL-5 cells were more responsive to both bovine and human TSH than were human thyroid follicular cells maintained as primary monolayer cultures. Dose-response curves for cyclic AMP accumulation were parallel for a single cell type differentially incubated with human TSH (the First International Reference Preparation) and bovine TSH (Armour 'Thytropar') preparations. The relative potencies (units: IU) of bovine-human TSH were of the order of 2.0 when tested on both FRTL-5 cultures and primary human thyroid monolayers. This suggests that in the spectrum of structural differences between TSH receptors of different species, the discriminatory powers of the human and FRTL-5 cell TSH receptor are similar. Thus FRTL-5 cells form the basis of a bioassay system of considerable value in the study of human thyroid stimulators, as we demonstrate in an evaluation of two recent preparations of human TSH.

scholarly journals The new generation PFAS C6O4 does not produce adverse effects on thyroid cells in vitro

2020 ◽  
Author(s):  
F. Coperchini ◽  
L. Croce ◽  
P. Pignatti ◽  
G. Ricci ◽  
D. Gangemi ◽  
...  
Keyword(s):  
Adverse Effects ◽  
Cell Viability ◽  
Human Thyroid ◽  
Thyroid Cell ◽  
Ros Production ◽  
Thyroid Cells ◽  
Time Points ◽  
Rat Thyroid ◽  
Long Chain

Abstract Purpose Per- and poly-fluoroalkyl-substances (PFASs) are synthetic compounds that raised concern due to their potential adverse effects on human health. Long-chain PFAS were banned by government rules in many states, and thus, new emerging PFAS were recently introduced as substitutes. Among these, Perfluoro{acetic acid, 2-[(5-methoxy-1,3-dioxolan-4-yl)oxy]}, ammonium salt (C6O4) was recently introduced to produce a range of food contact articles and literature data about this compound are scanty. The aim of this study was to evaluate the in vitro effects of exposure to C6O4, compared with PFOA and PFOS on thyroid cells. Methods FRTL5 rat-thyroid cell lines and normal human thyroid cells (NHT) were incubated with increasing concentrations of C6O4 for 24, 48, 72, and 144 h to assess cell viability by WST-1. Cell viability was confirmed by AnnexinV/PI staining. Long-chain PFAS (PFOA and PFOS) were used at same concentrations as positive controls. The proliferation of cells exposed to C6O4, PFOA, and PFOS was measured by staining with crystal violet and evaluation of optical density after incubation with SDS. Changes in ROS production by FRTL5 and NHT after exposure to C6O4 at short (10, 20, and 30 min) and long-time points (24 h) were evaluated by cytofluorimetry. Results C6O4 exposure did not modify FRTL5 and NHT cell viability at any concentration and/or time points with no induction of necrosis/apoptosis. At difference, PFOS exposure reduced cell viability of FRTL5 while and NHT, while PFOA only in FRTL5. FRTL5 and NHT cell proliferation was reduced by incubation with by PFOA and PFOS, but not with C6O4. ROS production by NHT and FRTL5 cells was not modified after C6O4 exposure, at any time/concentration tested. Conclusions The present in vitro study constitutes the first evaluation of the potential adverse effects of the new emerging PFAS C6O4 in cultured rat and human thyroid cells, suggesting its safety for thyroid cells in vitro.

FK506 inhibits phytohemagglutinin-, but not interferon-γ-, induced HLA-DR antigen expression and accessory cell function on primary cultured human thyroid cells

1993 ◽  
Vol 129 (6) ◽  
pp. 579-584 ◽  
Author(s):  
Masayuki Sato ◽  
Yuji Hiromatsu ◽  
Kiyoko Tanaka ◽  
Noriko Ishisaka ◽  
Kyohei Nonaka
Keyword(s):  
Cell Function ◽  
Antigen Expression ◽  
Interferon Γ ◽  
Human Thyroid ◽  
Accessory Cell ◽  
Thyroid Cell ◽  
Dependent Manner ◽  
Thyroid Cells ◽  
Hla Dr ◽  
Ifn Γ

We investigated the effects of FK506, a novel immunosuppressive agent, on the phytohemagglutinin (PHA) or interferon-γ (IFN-γ)-induced expression of HLA-DR antigen, accessory cell function and proliferation of primary cultured human thyroid cells. Primary cultured thyroid cells from patients with Graves' disease were incubated for 3 days with PHA in concentrations in the range 1–50 mg/l or with 200 kU/l of IFN-γ, in the presence or absence of FK506. The surface expression of HLA-DR antigen was measured by flow cytometry. Accessory cell function of thyroid cells was assessed by the incorporation of [3H]thymidine to T cells in the presence of 0.1–1.0 μg/l staphylococcus enterotoxin B (SEB). The proliferation of thyroid cells was determined from [3H]thymidine incorporation assays. FK506 inhibited the induction of HLA-DR antigen expression by PHA on thyroid cells in a dose-dependent manner, but did not inhibit that by IFN-γ. Polyclonal anti-IFN-γ antibody partly inhibited the PHA-induced HLA-DR antigen expression on thyroid cells. Phytohemagglutinin enhanced the SEB-mediated accessory cell function of thyroid cells. FK506 inhibited the accessory cell function induced by PHA. FK506 alone did not directly affect the thyroid cell proliferation, although it ameliorated the thyroid cell growth suppressed by PHA. Our data suggest that FK506 suppresses the HLA-DR antigen expression induced by PHA and the subsequent accessory cell function on thyroid cells via the inhibition of T lymphocytes present in the primary culture.

A possible role for calmodulin in human thyroid cell metabolism

1983 ◽  
Vol 99 (2) ◽  
pp. 251-260 ◽  
Author(s):  
C. A. Ollis ◽  
S. MacNeil ◽  
S. W. Walker ◽  
B. L. Brown ◽  
R. M. Sharrard ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Polyacrylamide Gel Electrophoresis ◽  
Sodium Dodecyl ◽  
Biologically Active ◽  
Human Thyroid ◽  
Thyroid Cell ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Thyroid Cells ◽  
Cell Extracts

A protein which shared several characteristics with authentic calmodulin was extracted from human thyroid homogenates. The protein bound to fluphenazine–Sepharose and could be specifically eluted using EGTA. The eluted protein had a u.v. spectrum characteristic of calmodulin and migrated like authentic calmodulin with a calcium-dependent shift on sodium dodecyl sulphate polyacrylamide-gel electrophoresis. Calmodulin in thyroid cell extracts was shown to be biologically active, measured by its ability to activate a calmodulin-deficient cyclic GMP phosphodiesterase; this activation could be inhibited by trifluoperazine. A possible role for calmodulin in the action of TSH on the thyroid was demonstrated by studying the effects of phenothiazines and the naphthalene sulphonamide, W7, a more specific calmodulin inhibitor, on TSH-stimulated cyclic AMP levels in cultured thyroid cells. The phenothiazines and W7 were found to inhibit the accumulation of cyclic AMP in response to TSH in a concentration-dependent manner although low concentrations of W7 enhanced TSH-stimulated cyclic AMP accumulation.

scholarly journals Serum Withdrawal-Induced Apoptosis in Thyroid Cells Is Caused by Loss of Fibronectin-Integrin Interaction*

2000 ◽  
Vol 85 (3) ◽  
pp. 1188-1193 ◽  
Author(s):  
Tiziana Di Matola ◽  
Frank Mueller ◽  
Gianfranco Fenzi ◽  
Guido Rossi ◽  
Maurizio Bifulco ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Present Report ◽  
Annexin V ◽  
Cell Types ◽  
Human Thyroid ◽  
Thyroid Cell ◽  
Thyroid Cells ◽  
Serum Withdrawal ◽  
Induced Apoptosis ◽  
Rat Thyroid

Abstract In some cell types, including a fetal thyroid cell line, denial of adhesion to extracellular matrix induces a type of apoptosis called anoikis. Serum withdrawal in dog and transformed rat thyroid cells also induces programmed cell death. Because serum can stimulate cells to produce some components of the extracellular matrix, it was of interest to determine the role of the matrix in the apoptosis induced by serum withdrawal in normal human thyroid cells in primary culture. The present report demonstrates that thyroid cells selectively produce and deposit insoluble fibronectin (FN) only when stimulated by serum. Adhesion in the presence of serum is dependent upon integrin-FN interaction. Serum withdrawal determines a degradation of the insoluble FN deposited and a detachment of the cells from the plates. In these conditions, cells undergo anoikis, demonstrated by DNA fragmentation and annexin V staining. Apoptosis was prevented by exogenous FN immobilized onto the plates. These results indicate that serum withdrawal induces apoptosis in human thyroid cells, determining FN degradation and loss of cell-matrix adhesion.

scholarly journals EGF and TGF-1 Effects on Thyroid Function

2011 ◽  
Vol 2011 ◽  
pp. 1-13 ◽  
Author(s):  
Gabriella Mincione ◽  
Maria Carmela Di Marcantonio ◽  
Chiara Tarantelli ◽  
Sonia D'Inzeo ◽  
Arianna Nicolussi ◽  
...  
Keyword(s):  
Growth Factors ◽  
Cell Lines ◽  
Cross Talk ◽  
Early Stage ◽  
Tumor Promoter ◽  
Human Thyroid ◽  
Thyroid Cell ◽  
Thyroid Tumors ◽  
Thyroid Cells ◽  
Rat Thyroid

Normal epithelial thyroid cells in culture are inhibited by TGF-1. Instead, transformed thyroid cell lines are frequently resistant to its growth inhibitory effect. Loss of TGF- responsiveness could be due to a reduced expression of TGF- receptors, as shown in transformed rat thyroid cell lines and in human thyroid tumors, or to alterations of other genes controlling TGF- signal transduction pathway. However, in thyroid neoplasia, a complex pattern of alterations occurring during transformation and progression has been identified. Functionally, TGF-1 acts as a tumor suppressor in the early stage of transformation or as a tumor promoter in advanced cancer. This peculiar pleiotropic behaviour of TGF- may result from cross-talk with signalling pathways mediated by other growth factors, among which EGF-like ligands play an important role. This paper reports evidences on TGF-1 and EGF systems in thyroid tumors and on the cross-talk between these growth factors in thyroid cancer.

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