Thyroid-stimulating hormone increases active transport of perchlorate into thyroid cells

2008 ◽  
Vol 294 (4) ◽  
pp. E802-E806 ◽  
Author(s):  
Neil Tran ◽  
Liza Valentín-Blasini ◽  
Benjamin C. Blount ◽  
Caroline Gibbs McCuistion ◽  
Mike S. Fenton ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Active Transport ◽  
Measurement Techniques ◽  
Thyroid Stimulating Hormone ◽  
Dependent Manner ◽  
Iodide Uptake ◽  
Thyroid Cells ◽  
Rat Thyroid ◽  
Inhibit Cell Proliferation ◽  
Stimulating Hormone

Perchlorate blocks thyroidal iodide transport in a dose-dependent manner. The human sodium/iodide symporter (NIS) has a 30-fold higher affinity for perchlorate than for iodide. However, active transport of perchlorate into thyroid cells has not previously been demonstrated by direct measurement techniques. To demonstrate intracellular perchlorate accumulation, we incubated NIS-expressing FRTL-5 rat thyroid cells in various concentrations of perchlorate, and we used a sensitive ion chromatography tandem mass spectrometry method to measure perchlorate accumulation in the cells. Perchlorate caused a dose-related inhibition of 125-iodide uptake at 1–10 μM. The perchlorate content from cell lysate was analyzed, showing a higher amount of perchlorate in cells that were incubated in medium with higher perchlorate concentration. Thyroid-stimulating hormone increased perchlorate uptake in a dose-related manner, thus supporting the hypothesis that perchlorate is actively transported into thyroid cells. Incubation with nonradiolabeled iodide led to a dose-related reduction of intracellular accumulation of perchlorate. To determine potential toxicity of perchlorate, the cells were incubated in 1 nM to 100 μM perchlorate and cell proliferation was measured. Even the highest concentration of perchlorate (100 μM) did not inhibit cell proliferation after 72 h of incubation. In conclusion, perchlorate is actively transported into thyroid cells and does not inhibit cell proliferation.

scholarly journals Differential effect of thyroid-stimulating hormone (TSH) on intracellular free calcium and cAMP in cells transfected with the human TSH receptor

1998 ◽  
Vol 157 (3) ◽  
pp. 415-424 ◽  
Author(s):  
RA Metcalfe ◽  
C Findlay ◽  
WR Robertson ◽  
AP Weetman ◽  
S Mac Neil
Keyword(s):  
Adenylate Cyclase ◽  
Intracellular Calcium ◽  
Single Cells ◽  
Thyroid Stimulating Hormone ◽  
Tsh Receptor ◽  
Similar Data ◽  
Thyroid Cells ◽  
Single Addition ◽  
Rat Thyroid ◽  
Stimulating Hormone

The thyroid-stimulating hormone (TSH) binds to a receptor which activates adenylate cyclase and elevates cAMP concentration. In addition, effects of TSH on intracellular calcium and inositol phosphate accumulation have been reported. However, the mechanism of TSH-stimulated accumulation of inositol phosphates and elevation of calcium levels is unresolved. Previous work from this laboratory has shown TSH to cause acute transient increases in intracellular calcium in pig, human and FR TL-5 rat thyroid cells as well as in cell transfected with the human TSH receptor (JPO9 cells) in some (but not all) experiments. The aim of this study was to investigate the variability of the calcium response to TSH in JPO9 cells to learn more about the nature of this calcium signal induction. Calcium responses to TSH were determined using the fluorochrome fura-2 in both monolayers of adherent cells and adherent single cells. The responses to a single addition and to repetitive additions of TSH were compared. We also determined the cAMP response to TSH using these two protocols of TSH addition. Our data show that, whereas the cAMP response to TSH is highly predictable and consistent and does not require multiple exposures to TSH, cells were unlikely to respond to TSH with an increase in calcium unless they received multiple challenges with the hormone. A single addition of 10 mU/ml TSH failed to increase calcium in any of 40 single cells examined and in only 4 of 15 monolayers of cells (27%) examined; in contrast, 10 of 12 monolayers eventually responded with an increase in calcium after multiple exposure to TSH and 18 of 67 single cells. Similar data were obtained whether calcium was measured in single cells or in populations of cells. We also demonstrated cooperativity between an adenosine derivative, N6-(L-2-phenylisopropyl)adenosine, and TSH such that their co-administration resulted in a consistent and marked elevation in calcium levels not achieved with either agonist alone. In summary, we suggest that the coupling between the TSH receptor and the intracellular signalling system that leads to activation of intracellular calcium in JPO9 cells requires repetitive stimulation or the influence of other agonists, in contrast with the coupling between the TSH receptor and activation of the adenylate cyclase enzyme.

Control of thyroglobulin secretion from the rat thyroid gland

1984 ◽  
Vol 101 (1) ◽  
pp. 107-111 ◽  
Author(s):  
E. G. Black ◽  
M. C. Sheppard ◽  
R. Hoffenberg
Keyword(s):  
Thyroid Stimulating Hormone ◽  
Dependent Manner ◽  
Serum Thyroglobulin ◽  
Thyroid Cells ◽  
Normal Rat ◽  
Rat Thyroid ◽  
Dose Dependent ◽  
Rat Thyroid Gland

ABSTRACT Serum thyroglobulin (Tg), measured by radioimmunoassay, was high in 6-propylthiouracil (PTU)-treated rats but low in thyroxine (T4)-treated animals compared with euthyroid controls. Thyroid-stimulating hormone (TSH) stimulated Tg release in vitro from enzymatically dispersed normal rat thyroid cells in a dose-dependent manner. Thyroid cells prepared from T4-treated animals behaved similarly to cells from control rats, whereas in vitro basal release of Tg from thyroid cells prepared from PTU-treated animals was high and the response to TSH was lost. Our data confirm the TSH dependency of Tg release in vivo and in vitro and our system provides a means of studying the control of Tg secretion in vitro. J. Endocr. (1984) 101, 107–111

Induction of manganese superoxide dismutase by thyroid stimulating hormone in rat thyroid cells

FEBS Letters ◽  
1997 ◽  
Vol 416 (1) ◽  
pp. 69-71 ◽  
Author(s):  
Shozo Nishida ◽  
Takayuki Nakano ◽  
Saori Kimoto ◽  
Takashi Kusunoki ◽  
Keiichiro Suzuki ◽  
...  
Keyword(s):  
Superoxide Dismutase ◽  
Manganese Superoxide Dismutase ◽  
Thyroid Stimulating Hormone ◽  
Thyroid Cells ◽  
Manganese Superoxide ◽  
Rat Thyroid ◽  
Stimulating Hormone

THE EFFECT OF PROPYLTHIOURACIL AND THYROID-STIMULATING HORMONE ON THE SURVIVAL OF RAT THYROID CELLS IN VIVO AND IN VITRO

1968 ◽  
Vol 41 (4) ◽  
pp. 577-591 ◽  
Author(s):  
J. W. SPEIGHT ◽  
W. I. BABA ◽  
G. M. WILSON
Keyword(s):  
Toxic Effect ◽  
Tritiated Thymidine ◽  
Thyroid Stimulating Hormone ◽  
Thyroid Cells ◽  
Rat Thyroid ◽  
Stimulating Hormone

SUMMARY The persistence of tritiated DNA ([3H]DNA) in the thyroids of rats given propylthiouracil (PTU) or PTU plus thyroxine was compared with that in control animals who received either no drugs or thyroxine alone. When only PTU was given, large goitres developed from which [3H]DNA was lost more rapidly than from thyroids of control animals. Administration of thyroxine with PTU led to only slight thyroidal enlargement, but the persistence of [3H]DNA was similarly reduced. The results suggested that PTU might have a toxic effect, reducing the lifespan of thyroid cells and this was further investigated using monolayer thyroid cultures. Thyroid-stimulating hormone (TSH) accelerated the incorporation of tritiated thymidine ([3H]TdR) into cultures, but when PTU was also given the uptake was retarded. PTU alone was less effective in inhibiting [3H]TdR incorporation. The persistence of [3H]DNA in thyroid cultures was unaffected by PTU and was decreased by TSH. When PTU and TSH were given together there was a greatly increased loss of isotope from the cells.

The inhibitory effect of iodide on growth of rat thyroid (FRTL-5) cells

1988 ◽  
Vol 119 (1) ◽  
pp. 145-151 ◽  
Author(s):  
Motoyasu Saji ◽  
Osamu Isozaki ◽  
Toshio Tsushima ◽  
Mariko Arai ◽  
Megumi Miyakawa ◽  
...  
Keyword(s):  
Cell Growth ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Camp Production ◽  
Iodide Uptake ◽  
Concentration Dependent Manner ◽  
Thyroid Cells ◽  
Camp Generation ◽  
Rat Thyroid ◽  
Sites Of Action

Abstract. The effect of iodide on growth of rat thyroid cells (FRTL-5) was studied. TSH-stimulated cell growth was inhibited by iodide in a concentration-dependent manner, and an effect of iodide was detected at 10−6 mol/l. KClO4 or 1-methylimidazole-2-thiol blocked the effect of iodide, suggesting that iodide uptake and its organification are required to produce the inhibitory effect of iodide on cell growth. Iodide not only decreased TSH-stimulated cAMP production in FRTL-5 cells but also cell growth induced by cAMP. These observations suggest that iodide inhibits TSH-stimulated growth of the cells by attenuating cAMP production and also by acting on the step(s) distal to cAMP generation. The inhibitory effect of iodide was also seen in growth stimulated by insulin, insulin-like growth factor-I or 12-O-tetradecanoyl phorbol 13-acetate, suggesting multiple sites of action of iodide in the process of growth of FRTL-5 cells.

Different isoforms of human pituitary thyroid-stimulating hormone have different relative biological activities

1992 ◽  
Vol 9 (3) ◽  
pp. 251-256 ◽  
Author(s):  
A. J. Pickles ◽  
N. Peers ◽  
W. R. Robertson ◽  
A. Lambert
Keyword(s):  
Cyclic Amp ◽  
Biological Activities ◽  
Thyroid Stimulating Hormone ◽  
Thymidine Uptake ◽  
Iodide Uptake ◽  
Human Pituitary ◽  
Thyroid Cells ◽  
Cyclic Amp Accumulation ◽  
Reference Preparation ◽  
Stimulating Hormone

ABSTRACT The relationship between the immunological and biological activities of thyroid-stimulating hormone (TSH) isoforms present in the three human pituitary preparations 68/38 (1st IRP), 80/558 (2nd IRP) and 63/14 (MRC Research Standard A) was investigated. The isoforms were separated by chromatofocusing. Six peaks of immunoactivity were detected in 80/558, with pI values (means±s.e.m.) of 6·6±0·1, 6·2±0·1, 5·9±0·1, 5·5±0·1, 5·2±0·1 and 4·9±0·1. Four peaks, with pi values of 6·8±0·1, 5·9±0·1, 5·5±0·1 and 5·2±0·1, were observed for 68/38. Standard 63/14 had five peaks, with pI values of 6·9±0·1, 6·4±0·1, 5·9±0·1, 5·4±0·1 and 4·9±0·1. For each standard, six fractions around the peak areas and at the top and bottom of the gradient were pooled and microconcentrated to <1·0ml. Microconcentrated TSH samples were assayed in three TSH bioassays based upon FRTL-5 thyroid cells, utilizing cyclic AMP accumulation, iodide and thymidine uptake as end-points and standard 80/558 as reference preparation. The more acidic forms of TSH showed a higher biological: immunological (B: I) ratio for cyclic AMP accumulation with, for example, 63/14 having a maximum of 3·7 (pI 4·9) and a minimum of <0·7 (pI 6·9). In contrast, the maximum and minimum B: I ratios for iodide uptake for 63/14 were 3·8 (pI 6·9) and <0·8 (pI 4·6), and for thymidine uptake, maximum and minimum ratios were 7·2 (pI 6·9) and 1·1 (pI 4·6) respectively. In conclusion, the acidic forms of TSH stimulated cyclic AMP accumulation more than the alkaline forms, whereas the opposite was shown for iodide uptake and thymidine uptake.

scholarly journals Thyroid-stimulating hormone stimulates increases in inositol phosphates as well as cyclic AMP in the FRTL-5 rat thyroid cell line

1987 ◽  
Vol 247 (3) ◽  
pp. 519-524 ◽  
Author(s):  
J B Field ◽  
P A Ealey ◽  
N J Marshall ◽  
S Cockcroft
Keyword(s):  
Cyclic Amp ◽  
Cell Line ◽  
Inositol Phosphates ◽  
Inositol Phosphate ◽  
Thyroid Stimulating Hormone ◽  
Thyroid Cell ◽  
Dependent Manner ◽  
Thyroid Cell Line ◽  
Rat Thyroid ◽  
Stimulating Hormone

Studies were conducted to determine whether thyroid-stimulating hormone (TSH; thyrotropin), a hormone known to increase cytosol concentrations of cyclic AMP, also stimulates the formation of inositol phosphates in thyroid cells. TSH and noradrenaline both stimulated [3H]inositol phosphate formation in a concentration-dependent manner in the rat thyroid cell line, FRTL-5 cells, which had been prelabelled with [3H]inositol. The threshold concentration of TSH required to stimulate inositol phosphate formation was more than 20 munits/ml, which is approx. 10(3)-fold greater than that required for cyclic AMP accumulation and growth in these cells. We also demonstrate that membranes prepared from FRTL-5 cells possess a guanine nucleotide-activatable polyphosphoinositide phosphodiesterase, which suggests that activation of inositide metabolism in these cells may be coupled to receptors by the G-protein, Gp. Our findings suggest that two second-messenger systems exist to mediate the action of TSH in the thyroid.

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.

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