Acute and chronic leptin effect upon in vivo and in vitro rat thyroid iodide uptake

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.

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Expression and function of the novel proto-oncogene PBF in thyroid cancer: a new target for augmenting radioiodine uptake

Journal of Endocrinology ◽

10.1530/joe-11-0064 ◽

2011 ◽

Vol 210 (2) ◽

pp. 157-163 ◽

Cited By ~ 13

Author(s):

Vicki E Smith ◽

Jayne A Franklyn ◽

Christopher J McCabe

Keyword(s):

Thyroid Cancer ◽

Current Data ◽

Subcellular Localisation ◽

Sodium Iodide Symporter ◽

Iodide Uptake ◽

Radioiodine Uptake ◽

Novel Target ◽

And Function

Pituitary tumor-transforming gene (PTTG)-binding factor (PBF; PTTG1IP) was initially identified through its interaction with the human securin, PTTG. Like PTTG, PBF is upregulated in multiple endocrine tumours including thyroid cancer. PBF is believed to induce the translocation of PTTG into the cell nucleus where it can drive tumourigenesis via a number of different mechanisms. However, an independent transforming ability has been demonstrated both in vitro and in vivo, suggesting that PBF is itself a proto-oncogene. Studied in only a limited number of publications to date, PBF is emerging as a protein with a growing repertoire of roles. Recent data suggest that PBF possesses a complex multifunctionality in an increasing number of tumour settings. For example, PBF is upregulated by oestrogen and mediates oestrogen-stimulated cell invasion in breast cancer cells. In addition to a possible role in the induction of thyroid tumourigenesis, PBF overexpression in thyroid cancers inhibits iodide uptake. PBF has been shown to repress sodium iodide symporter (NIS) activity by transcriptional regulation of NIS expression through the human NIS upstream enhancer and further inhibits iodide uptake via a post-translational mechanism of NIS governing subcellular localisation. This review discusses the current data describing PBF expression and function in thyroid cancer and highlights PBF as a novel target for improving radioiodine uptake and thus prognosis in thyroid cancer.

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In vivo effects of flavonoid EMD 21388 on thyroid hormone secretion and metabolism in rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1991.261.2.e227 ◽

1991 ◽

Vol 261 (2) ◽

pp. E227-E232 ◽

Cited By ~ 3

Author(s):

J. P. Schroder-van der Elst ◽

D. van der Heide ◽

J. Kohrle

Keyword(s):

Thyroid Hormone ◽

Hormone Secretion ◽

Male Rats ◽

Intact Male ◽

Hormone Production ◽

Iodide Uptake ◽

Brown Adipose ◽

In Vivo Effects

In vitro, the synthetic flavonoid EMD 21388 appears to be a potent inhibitor of thyroxine (T4) 5'-deiodinase and diminishes binding of T4 to transthyretin. In this study, in vivo effects of long-term administration of EMD 21388 on thyroid hormone production and metabolism were investigated. Intact male rats received EMD 21388 (20 mumol.kg body wt-1.rat-1.day-1) for 14 days. [125I]T4 and 3,5,3'-[131I]triiodotyronine (T3) were infused continuously and intravenously in a double-isotope protocol for the last 10 and 7 days, respectively. EMD 21388 decreased plasma thyroid hormone concentrations, but thyrotropin levels in plasma and pituitary did not change. Plasma clearance rates for T4 and T3 increased. Thyroidal T4 secretion was diminished, but T3 secretion was elevated. Extrathyroidal T3 production by 5'-deiodination was lower. T4 concentrations were markedly lower in all tissues investigated. Total tissue T3 was lower in brown adipose tissue, brain, cerebellum, and pituitary, tissues that express the type II 5'-deiodinase isozyme due to decreased local T3 production. Most tissues showed increased tissue/plasma ratios for T4 and T3. These results indicate that this flavonoid diminished T4 and increased T3 secretion by the thyroid, probably in analogy with other natural flavonoids, by interference with one or several steps between iodide uptake, organification, and hormone synthesis.

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

Journal of Endocrinology ◽

10.1677/joe-08-0123 ◽

2008 ◽

Vol 198 (2) ◽

pp. 301-307 ◽

Cited By ~ 4

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.

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Ultrastructure of blebbing and phagocytosis of blebs by hyperplastic thyroid epithelial cells in vivo.

The Journal of Cell Biology ◽

10.1083/jcb.72.3.584 ◽

1977 ◽

Vol 72 (3) ◽

pp. 584-594 ◽

Cited By ~ 31

Author(s):

J D Zeligs ◽

S H Wollman

Keyword(s):

Thyroid Gland ◽

Epithelial Cells ◽

Cultured Cells ◽

Ultrastructural Organization ◽

Contractile Ring ◽

Phagocytic Process ◽

Different Types ◽

Rat Thyroid

In addition to pseudopods, somewhat pleomorphic blebs were consistently found protruding from the apical surfaces of hyperplastic rat thyroid epithelial cells into the follicular lumens in vivo. Many blebs were knobby, roughly hemispherical protrusions, with a diameter of 2-3 mum. Such blebs had a densely packed microfilamentous core and contained numerous apparent ribosomes. They were morphologically similar to blebs that have been observed in a variety of cultured cells. Other blebs were larger, more elongate, and less knobby, but had a similar ultrastructural organization. Blebs of all sizes appeared to be phagocytosed on some occasions by nearby epithelial cells. The phagocytic process involved partial engulfment of the bleb by a typical epithelial pseudopod, followed by an apparent pinching-off process, presumably resulting in the separation of the bleb from its cells or origin. The pinching-off process was associated with a band of approx. 6-nm diameter microfilaments that developed within the pseudopod cytoplasm surrounding the base of the bleb and is postulated to function as a contractile ring. The finding of blebbing is an intact tissue in vivo indicates that this phenomenon is not restricted to cultured cells, and thus tends to extend the significance of in vitro observations of the process. In relation to their occurrence in the hyperplastic thyroid gland in vivo, possible interconversions are considered between different types of blebs, and between blebs and pseudopods.

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2,3′,4,4′,5-Pentachlorobiphenyl Induced Thyrocyte Autophagy by Promoting Calcium Influx via Store-Operated Ca2+ Entry

Toxicological Sciences ◽

10.1093/toxsci/kfaa116 ◽

2020 ◽

Vol 177 (2) ◽

pp. 483-493

Author(s):

Li Wang ◽

Wenli Xu ◽

Qi Zhou ◽

Bojin Xu ◽

Yunlu Sheng ◽

...

Keyword(s):

Laser Scanning ◽

Calcium Influx ◽

Underlying Mechanism ◽

Laser Scanning Confocal Microscopy ◽

Thyroid Cell ◽

Dependent Manner ◽

Class Iii ◽

Rat Thyroid

Abstract PCB118, a 2,3′,4,4′,5-pentachlorobiphenyl, has been shown to destroy thyroidal ultrastructure and induce thyrocyte autophagy. Previously, we reported that PCB118 promoted autophagosome formation in vivo and in vitro, but more details remain to be revealed. To explore the underlying mechanism by which PCB118 regulates thyrocyte autophagy, Fischer rat thyroid cell line-5 (FRTL-5) cells were exposed to different doses of PCB118 at 0, 0.25, 2.5, and 25 nM for 0–48 h. Western blot analysis of autophagy-related proteins P62, BECLIN1, and LC3 demonstrated that PCB118 induced autophagy formation in dose- and time-dependent manner. Moreover, laser scanning confocal microscopy and flow cytometry showed PCB118 treatment led to time- and dose-dependent increase in intracellular calcium concentration ([Ca2+]i). Additionally, PCB118 promoted store-operated Ca2+ entry (SOCE) channel followed by significant increase of ORAI1 and STIM1 protein levels. On the other hand, PCB118 induced thyroidal autophagy via class III β-tubulin (TUBB3)/death-associated protein kinase 2 (DAPK2)/myosin regulatory light chain (MRLC)/autophagy-related 9A (ATG9A) pathway in FRTL-5 cells. Pretreatment with SOCE inhibitor SKF96365 reduced cytosolic Ca2+, ORAI1, STIM1, and BECLIN1 levels as well as LC3 II/LC3 I ratio, while increased P62 expression. SKF96365 also inhibited TUBB3/DAPK2/MRLC/ATG9A pathway in FRTL-5 cells treated by PCB118. Our results provide evidence that PCB118 may induce thyroidal autophagy through TUBB3-related signaling pathway, and these effects are likely to be regulated by calcium influx via SOCE channel.

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Reestablishment of In Vitro and In Vivo Iodide Uptake by Transfection of the Human Sodium Iodide Symporter (hNIS) in a hNIS Defective Human Thyroid Carcinoma Cell Line

Thyroid ◽

10.1089/thy.2000.10.939 ◽

2000 ◽

Vol 10 (11) ◽

pp. 939-943 ◽

Cited By ~ 36

Author(s):

Jan W.A. Smit ◽

Janny P. Schröder-van der Elst ◽

Marcel Karperien ◽

Ivo Que ◽

Gabri van der Pluijm ◽

...

Keyword(s):

Thyroid Carcinoma ◽

Cell Line ◽

Sodium Iodide ◽

Carcinoma Cell ◽

Human Thyroid ◽

Sodium Iodide Symporter ◽

Iodide Uptake ◽

Thyroid Carcinoma Cell

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The Flavonoid Quercetin Induces AP-1 Activation in FRTL-5 Thyroid Cells

Antioxidants ◽

10.3390/antiox8050112 ◽

2019 ◽

Vol 8 (5) ◽

pp. 112 ◽

Cited By ~ 2

Author(s):

Cesidio Giuliani

Keyword(s):

Binding Site ◽

Thyroid Function ◽

Thyroid Cell ◽

Consensus Binding Site ◽

Thyroid Cells ◽

Basal Activity ◽

Reporter Vector ◽

Rat Thyroid

Previous studies have shown that quercetin inhibits thyroid function both in vitro and in vivo. An attempt to evaluate the effect of quercetin at the promoter level of the thyroid-specific genes led to the observation that this compound induces the basal activity of the reporter vector. Therefore, the action of quercetin has been evaluated on the basal activity of several reporter vectors: The PGL3 basic, promoter and control vectors from Promega, and a pSV-based chloramphenicol acetyltransferase (CAT) reporter vector. In the Fisher Rat Thyroid cell Line FRTL-5 thyroid cells transiently transfected, quercetin 10 μM increased the basal activity of all the reporter vectors evaluated, although the degree of the effect was significantly different among them. The analysis of the difference among the regulatory regions of these vectors identified the activator protein 1 (AP-1) binding site as one of the potential sites involved in the quercetin effect. Electromobility shift assay experiments showed that the treatment with quercetin induced the binding of a protein complex to an oligonucleotide containing the AP-1 consensus binding site. This is the first study showing an effect of quercetin on AP-1 activity in thyroid cells. Further studies are in progress to understand the role of AP-1 activation in the effects of quercetin on thyroid function.

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IN-VITRO STUDIES OF NORMAL HUMAN THYROID CELLS: RESPONSES TO THYROTROPHIN AND DIBUTYRYL CYCLIC AMP

Journal of Endocrinology ◽

10.1677/joe.0.0720087 ◽

1977 ◽

Vol 72 (1) ◽

pp. 87-96 ◽

Cited By ~ 12

Author(s):

S. P. BIDEY ◽

P. MARSDEN ◽

J. ANDERSON ◽

C. G. McKERRON ◽

H. BERRY

Keyword(s):

Cyclic Amp ◽

Thyroid Tissue ◽

Three Dimensional ◽

Human Thyroid ◽

Dibutyryl Cyclic Amp ◽

Iodide Uptake ◽

Thyroid Cells ◽

Normal Human

SUMMARY Follicular cells isolated from normal human thyroid tissue have been cultured for up to 140 h with bovine thyrotrophin (TSH) or dibutyryl cyclic AMP (DBcAMP). Both compounds induced marked reorganization of the cells into three-dimensional follicular structures, whilst non-supplemented cells assumed a monolayer form. Cultures treated initially with TSH or DBcAMP showed a greater iodide uptake capacity, in comparison with unsupplemented cultures, in which iodide uptake was markedly diminished after 24 h. The release of tri-iodothyronine (T3) and thyroxine (T4) into the medium was determined by radioimmunoassay. Both TSH- and DBcAMP-treated cells showed a significant increase in iodothyronine output compared with unsupplemented control cells. In contrast to the 'classical' TSH-induced depression of the T4:T3 ratio in vivo, an increase in the ratio was observed for both TSH- and DBcAMP-supplemented cells in vitro. The ratio was also significantly greater after TSH than after DBcAMP, and possible implications of this finding are discussed.

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Evidence for a thyroid-inhibiting factor of adenohypophysial origin

American Journal of Physiology-Legacy Content ◽

10.1152/ajplegacy.1964.206.5.1145 ◽

1964 ◽

Vol 206 (5) ◽

pp. 1145-1150 ◽

Cited By ~ 1

Author(s):

Israel Posner ◽

Enrique Pimentel

Keyword(s):

Anterior Pituitary ◽

Inhibitory Effect ◽

In Vivo Studies ◽

Pituitary Extract ◽

Inhibiting Factor ◽

Rat Thyroid ◽

Tsh Stimulation ◽

Stimulation Of

Thyroids of normal or thyroxine ( T4)-pretreated rats were incubated in vitro in a serum medium containing I131. It was found that the addition of either a whole rat adenohypophysis, a crude rat anterior pituitary extract, or of commercial bovine thyrotrophin (TSH) to the medium caused a slight stimulation of I131 release and no apparent stimulation but rather an immediate and considerable inhibition of thyroid-I131 uptake. Preincubation of rat thyroid with crude anterior pituitary extract resulted in a prolonged inhibitory effect on the thyroid-I131 uptake. In vivo studies showed that shortly after TSH administration a similar inhibition of uptake occurred in normal rats, although allowing 24 hr for TSH stimulation brought about no change in iodine uptake in thyroids of normal and a marked increase in uptake by thyroids of T4-pretreated rats. The inhibition of thyroid-I131 uptake was assumed to have been caused either by TSH itself, or by a thyroid-inhibiting factor of adenohypophysial origin present in commercial TSH preparations as a contaminant.

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