Effects of ketoconazole on the iodide uptake by FRTL-5 cells

1992 ◽  
Vol 127 (5) ◽  
pp. 449-453 ◽  
Author(s):  
Sergio L Kohan ◽  
Carlota E Guillén ◽  
Esther M Pardes ◽  
Marcelo Junco ◽  
Roberto J Soto ◽  
...  
Keyword(s):  
Culture Medium ◽  
Endocrine System ◽  
Inhibitory Effect ◽  
Thyroid Cell ◽  
Iodide Uptake ◽  
Uptake Inhibition ◽  
Dual Action ◽  
Antimycotic Agent ◽  
Rat Thyroid ◽  
Dose Dependent

Ketoconazole is an imidazole derivative used as an antimycotic agent with reported effects on the endocrine system, but very little is known about its possible actions on thyroid function. Our purpose was to study the influence of this substance on the basal and TSH-stimulated iodide uptake in the rat thyroid cell strain FRTL-5. Ketoconazole (1–50 μmol/l) was shown to slightly increase the basal iodide uptake but, at higher concentrations (75–100 μmol/l), it sharply decreased iodide uptake below the basal levels. When the cells were cultured under bTSH stimulation (30 UI/l), the inhibitory effect of ketoconazole was exerted at concentrations as low as 25 μmol/l. This inhibition was observed even if it was added to the culture medium immediately before the Na125I addition. Forskolin, a stimulator of adenylate cyclase activity, was unable to prevent the iodide uptake inhibition. Low doses of ketoconazole increased cAMP concentrations. In the presence of TSH this effect was more evident in an inverse dose-dependent way. Because of its dual action, it can be assumed that ketoconazole could influence the iodide uptake in the FRTL-5 cells through more than one mechanism.

Effects of forskolin on the morphology and function of the rat thyroid cell strain, FRTL-5: comparison with the effects of thyrotrophin

1986 ◽  
Vol 111 (3) ◽  
pp. 397-NP ◽  
Author(s):  
K. Yun ◽  
S. Yamashita ◽  
K. Izumi ◽  
N. Yonemitsu ◽  
H. Sugihara
Keyword(s):  
Culture Medium ◽  
Morphological Changes ◽  
Cell Strain ◽  
Thyroid Cell ◽  
Dependent Manner ◽  
Camp System ◽  
Rat Thyroid ◽  
And Function ◽  
Cell Retraction ◽  
Dose Dependent

ABSTRACT The effect of diterpene forskolin, a potent stimulator of cyclic AMP (cAMP) in the rat thyroid cell strain FRTL-5, was compared with that of TSH. Forskolin stimulated both the release of cAMP into the culture medium and the accumulation of cAMP in the cytoplasm in a dose-dependent manner, within the range of 0·1–1000 μmol/l. Maximum cAMP concentrations were reached within 15 min of stimulation with forskolin. This is comparable with the effects of TSH. Forskolin also induced morphological changes in cultures of FRTL-5 cells, producing conspicuous cell retraction with arborization and numerous microvilli on the cell surface, specific reorganization of the microfilaments and modulation of the distribution of tubulin and fibronectin. Morphological changes induced by forskolin were always observed 20 to 30 min earlier, and in a higher percentage of cells, than the changes induced by TSH. Cell proliferation, however, was stimulated more effectively by TSH than by forskolin. These observations suggest that TSH might exert its effect on the morphology and growth of FRTL-5 cells, at least in part, through cAMP. The control of morphology and growth might not, however, be regulated solely by the adenylate cyclase and cAMP system. J. Endocr. (1986) 111, 397–405

scholarly journals Iodide symporter gene expression in normal and transformed rat thyroid cells

1999 ◽  
pp. 447-451 ◽  
Author(s):  
F Trapasso ◽  
R Iuliano ◽  
E Chiefari ◽  
F Arturi ◽  
A Stella ◽  
...  
Keyword(s):  
Gene Expression ◽  
Cell Lines ◽  
Inhibitory Effect ◽  
Mrna Levels ◽  
Iodide Uptake ◽  
Thyroid Cells ◽  
Transformed Cell ◽  
Nis Gene ◽  
Rat Thyroid ◽  
Transformed Cell Lines

OBJECTIVE: Decrease or loss of the Na+/I- symporter (NIS) activity profoundly affects the suitability of the use of radioiodine to detect or treat metastatic thyroid tissues. The aim of our study was to verify whether specific oncogene abnormalities were responsible for the alteration in NIS activity in thyroid cells. DESIGN AND METHODS: Expression of the NIS gene was investigated by Northern blot analysis in normal and in some oncogene-transformed cell lines with different degrees of malignancy which had lost the iodide uptake ability. RESULTS: NIS gene expression was up-regulated by TSH in a dose-dependent and time-dependent way in normal PC Cl 3 cells. The same effect was observed by activating the cAMP-dependent pathway by forskolin. Conversely, insulin and 12-O-tetradecanoylphorbol-13-acetate (TPA) showed a partial inhibitory effect on NIS gene expression. The oncogene-transformed cell lines PC v-erbA, PC HaMSV, PC v-raf, and PC E1A cells showed reduced NIS mRNA levels compared with the normal PC Cl 3 cells. Conversely, an almost complete absence of NIS gene expression was found in PC RET/PTC, PC KiMSV, PC p53(143ala), and PC PyMLV cell lines. CONCLUSIONS: Our data show that oncogene activation could play a role in affecting the iodide uptake ability in thyroid tumoral cells; different mechanisms are involved in the oncogene-dependent loss of NIS activity in transformed thyroid cells.

scholarly journals Iodide excess regulates its own efflux: a possible involvement of pendrin

2016 ◽  
Vol 310 (7) ◽  
pp. C576-C582 ◽  
Author(s):  
Jamile Calil-Silveira ◽  
Caroline Serrano-Nascimento ◽  
Peter Andreas Kopp ◽  
Maria Tereza Nunes
Keyword(s):  
Plasma Membrane ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Sodium Iodide ◽  
Inhibitory Effect ◽  
Membrane Insertion ◽  
Sodium Iodide Symporter ◽  
Iodide Uptake ◽  
Hormone Synthesis ◽  
Rat Thyroid

Adequate iodide supply and metabolism are essential for thyroid hormones synthesis. In thyrocytes, iodide uptake is mediated by the sodium-iodide symporter, but several proteins appear to be involved in iodide efflux. Previous studies demonstrated that pendrin is able to mediate apical efflux of iodide in thyrocytes. Acute iodide excess transiently impairs thyroid hormone synthesis, a phenomenon known as the Wolff-Chaikoff effect. Although the escape from this inhibitory effect is not completely understood, it has been related to the inhibition of sodium-iodide symporter-mediated iodide uptake. However, the effects of iodide excess on iodide efflux have not been characterized. Herein, we investigated the consequences of iodide excess on pendrin abundance, subcellular localization, and iodide efflux in rat thyroid PCCl3 cells. Our results indicate that iodide excess increases pendrin abundance and plasma membrane insertion after 24 h of treatment. Moreover, iodide excess increases pendrin half-life. Finally, iodide exposure also increases iodide efflux from PCCl3 cells. In conclusion, these data suggest that pendrin may have an important role in mediating iodide efflux in thyrocytes, especially under conditions of iodide excess.

scholarly journals Inhibition of in vitro maturation of equine oocytes by interleukin 1 beta via specific IL-1 receptors

Reproduction ◽  
2003 ◽  
pp. 509-515 ◽  
Author(s):  
A Martoriati ◽  
M Caillaud ◽  
G Goudet ◽  
N Gerard
Keyword(s):  
Oocyte Maturation ◽  
In Vitro Maturation ◽  
Culture Medium ◽  
Interleukin 1 ◽  
Inhibitory Effect ◽  
Interleukin 1 Beta ◽  
Nuclear Maturation ◽  
Epidermal Growth ◽  
Dose Dependent

Interleukin 1 beta (IL-1 beta) inhibits the LH-induced resumption of meiosis of equine oocytes in vitro. The present study was performed to clarify this inhibitory effect of IL-1 beta by testing increasing concentrations of IL-1 beta, and by measuring the effect of addition of IL-1 receptor antagonist (IL-1RA) to the culture medium. The effect of IL-1 beta on epidermal growth factor (EGF)-induced resumption of meiosis was also studied. Cumulus-oocyte complexes (COCs) were collected from subordinate follicles on ovaries obtained from an abattoir. In five distinct experiments, COCs were cultured for 30 h and nuclear maturation of oocytes was evaluated by DNA staining. In Expt 1, seven different media were tested: medium 1 (TCM199+BSA); medium 2 (medium 1+50 ng IL-1 beta ml(-1)); medium 3 (medium 1+eLH); and media 4, 5, 6 and 7 (medium 3 containing 0.1, 1.0, 10.0 and 50.0 ng IL-1 beta ml(-1), respectively). In Expt 2, four different media were tested: medium 1 (TCM199+BSA+eLH); medium 2 (medium 1+50 ng IL-1 beta ml(-1)); and media 3 and 4 (medium 2+IL-1RA at 50 and 100 ng ml(-1), respectively). In Expt 3, three different media were tested: medium 1 (TCM199+BSA+eLH); medium 2 (medium 1+50 ng IL-1RA ml(-1)); and medium 3 (medium 2+50 ng IL-1 beta ml(-1)). In Expt 4, four different media were tested: medium 1 (TCM199+BSA+eLH); and media 2, 3 and 4 (medium 1+IL-1RA at 50, 100 and 150 ng ml(-1), respectively). In Expt 5, three different media were tested: medium 1 (TCM199+BSA+EGF); medium 2 (medium 1+50 ng IL-1 beta ml(-1)); and medium 3 (medium 2+50 ng IL-1RA ml(-1)). In Expt 1, LH alone induced an increase in the rate of in vitro maturation (IVM) of equine oocytes (P<0.05), whereas IL-1 beta alone did not have any effect compared with medium 1. IL-1 beta (50 ng ml(-1)) significantly inhibited the eLH-induced IVM of oocytes (P<0.05) compared with medium 3. A decrease in rate of maturation was observed from a concentration of 10 ng IL-1 beta ml(-1) onwards. In Expt 2, the presence of IL-1RA in the culture medium inhibited the effect of IL-1 beta and restored the rate of oocyte maturation (P<0.05) observed in the presence of LH alone. In Expts 3 and 4 it was demonstrated that IL-1RA alone had no positive effect on the eLH-induced rate of maturation. In Expt 5, IL-1 beta inhibited the EGF-induced resumption of meiosis (P<0.05). The addition of IL-1RA inhibited this effect and restored the rate of oocyte maturation (P<0.05) observed with EGF alone. In conclusion, the present data confirm the inhibitory effect of IL-1 beta on IVM of equine oocytes induced by eLH and demonstrate its inhibitory effect on EGF-induced oocyte maturation. The rate of maturation decreased in a dose-dependent way and the lowest rate of maturation was observed at 50 ng IL-1 beta ml(-1) (P<0.05). The use of IL-1RA inhibited these effects, demonstrating that the action of IL-1 beta is receptor-mediated. Moreover, the results clearly show that, in equine species, IL-1 beta is involved in the physiology of COCs by regulating resumption of meiosis.

Effects of somatostatin and serotonin on calcitonin secretion from cultured rat parafollicular cells

1988 ◽  
Vol 117 (2) ◽  
pp. 214-218 ◽  
Author(s):  
Toyoshi Endo ◽  
Tsukasa Saito ◽  
Takashi Uchida ◽  
Toshimasa Onaya
Keyword(s):  
Culture Medium ◽  
Secretory Granules ◽  
Calf Serum ◽  
Human Calcitonin ◽  
Dependent Manner ◽  
Parafollicular Cells ◽  
Thyroid Glands ◽  
Rat Thyroid ◽  
Dose Dependent ◽  
Calcitonin Secretion

Abstract. A primary culture of mammalian parafollicular cells was established from rat thyroid glands in order to investigate the effects of serotonin and somatostatin on calcitonin secretion. Minced rat thyroid glands were dissociated with collagenase and cultured in a Ham's F-12K medium supplemented with calf serum (5%), insulin (1.3 × 10−6 mol/l), hydrocortisone (10−8 mol/l), transferrin (6.1 × 10−9 mol/l), and glycyl-L-histidyl-L-lysin (2.5 × 10−8 mol/l). Immunohistochemical peroxidase-antiperoxidase method revealed that the cultured parafollicular cells were immunopositive for human calcitonin, and electron microscopy demonstrated the existence of dense secretory granules in the cultured parafollicular cells. Addition of the Ca2+ to the culture medium stimulated calcitonin secretion from the cells dose-dependently as measured by radioimmunoassay. Pre-incubation of serotonin with the cells produced higher calcitonin levels in a dose-dependent manner. On the other hand, pre-incubation of somatostatin with the cells significantly inhibited calcitonin secretion.

Inhibitory Effect of Tetrandrine on the Proliferation of Human Dermal Fibroblasts Derived from Hypertrophic Scars

2011 ◽  
Vol 268-270 ◽  
pp. 838-840
Author(s):  
De Wu Liu ◽  
Xiang Hu ◽  
De Ming Liu ◽  
Ping Zou
Keyword(s):  
Hypertrophic Scar ◽  
Culture Medium ◽  
Inhibitory Effect ◽  
Dermal Fibroblasts ◽  
Dependent Manner ◽  
Human Dermal Fibroblasts ◽  
Hypertrophic Scars ◽  
Result Show ◽  
Dose Dependent

Tetrandrine can inhibit the proliferation and collagen synthesis of fibroblasts in lung and liver tissue confirmed by a series of clinical research. In this chapter, we investigated the effect of Tetrandrine on the proliferation of human dermal fibroblasts derived from hypertrophic scars. The dermal fibroblasts were isolated from human hypertrophic scar tissues and cultured in vitro. Tetrandrine with different concentration were added to culture medium respectively. The proliferative activities were determined. The result show that when the concentration of added Tetrandrine increased from 5μg/ml to 80μg/ml, the proliferative activities of cultured dermal fibroblasts were decreased gradually in dose-dependent manner. It conclusions that Tetrandrine can obviously inhibit the proliferation of human dermal fibroblasts derived from hypertrophic scars.

scholarly journals Bisphenol A increases hydrogen peroxide generation by thyrocytes both in vivo and in vitro

2018 ◽  
Vol 7 (11) ◽  
pp. 1196-1207 ◽  
Author(s):  
Maurício Martins da Silva ◽  
Lueni Lopes Felix Xavier ◽  
Carlos Frederico Lima Gonçalves ◽  
Ana Paula Santos-Silva ◽  
Francisca Diana Paiva-Melo ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Bisphenol A ◽  
Thyroid Cell ◽  
Mrna Levels ◽  
Iodide Uptake ◽  
Hydrogen Peroxide Generation ◽  
Rat Thyroid ◽  
The Impact

Bisphenol A (BPA) is the most common monomer in polycarbonate plastics and an endocrine disruptor. Though some effects of BPA on thyroid hormone (TH) synthesis and action have been described, the impact of this compound on thyroid H2O2 generation remains elusive. H2O2 is a reactive oxygen species (ROS), which could have deleterious effect on thyrocytes if in excess. Therefore, herein we aimed at evaluating the effect of BPA exposition both in vivo and in vitro on H2O2 generation in thyrocytes, besides other essential steps for TH synthesis. Female Wistar rats were treated with vehicle (control) or BPA 40 mg/kg BW for 15 days, by gavage. We then evaluated thyroid iodide uptake, mediated by sodium-iodide symporter (NIS), thyroperoxidase (TPO) and dual oxidase (DOUX) activities (H2O2 generation). Hydrogen peroxide generation was increased, while iodide uptake and TPO activity were reduced by BPA exposition. We have also incubated the rat thyroid cell line PCCL3 with 10−9 M BPA and evaluated Nis and Duox mRNA levels, besides H2O2 generation. Similar to that found in vivo, BPA treatment also led to increased H2O2 generation in PCCL3. Nis mRNA levels were reduced and Duox2 mRNA levels were increased in BPA-exposed cells. To evaluate the importance of oxidative stress on BPA-induced Nis reduction, PCCL3 was treated with BPA in association to N-acetylcysteine, an antioxidant, which reversed the effect of BPA on Nis. Our data suggest that BPA increases ROS production in thyrocytes, what could lead to oxidative damage thus possibly predisposing to thyroid disease.

Measurement of low concentrations of bovine thyrotrophin by iodide uptake and organification in porcine thyrocytes

1985 ◽  
Vol 106 (1) ◽  
pp. 13-NP ◽  
Author(s):  
S. C. J. Reader ◽  
B. Davison ◽  
J. G. Ratcliffe ◽  
W. R. Robertson
Keyword(s):  
Cyclic Amp ◽  
Culture Medium ◽  
Dose Range ◽  
Calf Serum ◽  
Inhibitory Effect ◽  
Maximal Response ◽  
Iodide Uptake ◽  
Free System ◽  
Cytochemical Bioassay ◽  
Dose Dependent Fashion

ABSTRACT Thyrocytes isolated from porcine thyroids by mechanical and enzymatic dispersion and cultured in Eagle's minimal essential medium, supplemented with 5% (v/v) fetal calf serum, glutamine and cortisol, formed a continuous monolayer within 48 h. This monolayer was without cytochemical peroxidase and diaphorase (NADPH reoxidation) activity. In the presence of bovine thyrotrophin (bTSH; 50 mu./l) the cells developed a follicular-like architecture which was maximal at 4 days before reverting back to a uniform monolayer at 6 days. There were no detectable changes in the total DNA content over this period. The follicular structures had marked diaphorase and peroxidase activity, the latter being apically distributed. Concomitant with follicle formation bTSH induced uptake and organification of iodide presented to the cells during the last 6 h of culture. The extent of this process depended on the dose of bTSH and the duration of stimulation. The most sensitive effects for both iodide uptake and organification occurred with 1 mu. bTSH/1 and were maximal with 100 mu./l. Uptake and organification were increased 20±8-fold and 9·6±2- fold (n = 10) respectively over the control with 100 mu./l and the doses of bTSH at which a half maximal response was seen (ED50) were 15±2 and 7±1 (s.d) mu./l (n = 10) respectively. On changing the culture medium to a serum-free system using HB101 culture medium the stimulation time for the most sensitive bTSH effect was reduced to 2·5 days. Moreover the sensitivity of iodide uptake to bTSH was dramatically increased being significantly stimulated by 0·1 mu./l, saturated with 10 mu./l, and having an ED50 of 7 ± 0·2 mu. bTSH/1 (n = 7). Over the dose range 0·1–10 mu. bTSH/l intra- and interassay coefficients of variation were 7%±1·5 (n = 15) and 11% ± 2·5 (n = 15) respectively. Cyclic AMP production in cultures incubated under similar conditions (i.e. after chronic TSH stimulation) was also stimulated by bTSH doses in the range 15·6–125 mu./l. Cells stimulated for 2·5 days with dibutyryl cyclic AMP (range 1 μmol/1–2 mmol/l) also actively concentrated iodide in a dose-dependent fashion. The presence of normal human serum in the medium yielded a progressive and dose-related decrease in TSH-stimulated iodide uptake. This inhibitory effect occurred with serum concentrations as low as 0·1%. In conclusion, a porcine cell culture system is described in which iodide uptake is significantly stimulated by 0·1 mu. bTSH/l, a sensitivity inferior only to that reported with the cytochemical bioassay. J. Endocr. (1985) 106, 13–20

Iodide autoregulation of functional and morphological differentiation events in the FRTL-5 rat thyroid cell strain

1990 ◽  
Vol 124 (1) ◽  
pp. 19-NP ◽  
Author(s):  
H. M. Beere ◽  
S. Tomlinson ◽  
S. P. Bidey
Keyword(s):  
Sodium Perchlorate ◽  
Morphological Differentiation ◽  
Cell Strain ◽  
Thyroid Cell ◽  
Intracellular Camp ◽  
Inhibitory Effects ◽  
Iodide Uptake ◽  
Camp Generation ◽  
Rat Thyroid

ABSTRACT The role of cyclic AMP (cAMP) attenuation in mediating the autoregulatory actions of iodide on thyroid cell iodide uptake and surface morphological responses to TSH was investigated in the rat thyroid cell strain FRTL-5. Preincubation of cells for 6 h with up to 1 mmol sodium iodide/1 led to a progressive reduction in both accumulation of cAMP and iodide uptake responses to TSH. Forskolin-mediated accumulation of cAMP and iodide uptake responses were similarly reduced after preincubation with iodide, whilst the iodide accumulation response to dibutyryl cAMP (dbcAMP) was unaffected. The inhibitory effects of iodide on TSH or forskolin-responsive iodide accumulation were not seen if preincubation was limited to 3 h, and were also abolished by the thionamide drug methimazole (1 mmol/l). Medium containing 1 μmol iodide/l prevented the appearance of the surface microvilli and pseudopodia normally observed after re-addition of TSH or forskolin, although cytoplasmic retraction was still apparent under such conditions. In contrast, iodide was without effect on the ability of dbcAMP (1 mmol/l) to induce cytoplasmic retraction and the formation of microvilli and pseudopodia. Inclusion of 1 mmol sodium perchlorate/l together with iodide during preincubation failed to prevent or reduce the suppression by iodide of either iodide uptake or surface morphological differentiation, suggesting that both aspects of autoregulation may involve surface actions of organified iodide. These observations indicate that in FRTL-5 cells, autoregulation by iodide of both the functional and surface morphological actions of TSH principally reflects the attenuating activities of organified iodide on intracellular cAMP generation. Journal of Endocrinology (1990) 124, 19–25

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