Effects of Tumor Necrosis Factor-α/Cachectin on Thyroid Hormone Metabolism in Mice*

Ozawa, Minoru; Sato, Kanji; Han, Doo Chol; Kawakami, Masanobu; Tsushima, Takahiro; Shizume, Kazuo

doi:10.1210/endo-123-3-1461

Cited by 111 publications

(46 citation statements)

References 29 publications

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“…In rat FRTL-5 thyroid cells, basal and TSH-induced D1 activity is inhibited by IL-1 , IL-6 and TNF , and D1 mRNA levels are reduced by IL-1 and IL-6, but not by TNF (Hashimoto et al 1995). In mouse liver D1 is stimulated by IL-1 (Fujii et al 1989) but is not affected by TNF (Ozawa et al 1988). However, in rat liver D1 is inhibited by TNF (Pang et al 1989, Tang et al 1995 in vivo but stimulated by TNF , IL-1 and IL-6 in vitro in rat liver 1 cells (Davies et al 1997).…”

Section: Discussionmentioning

confidence: 95%

“…Apart from D2, D1 is also expressed in the anterior pituitary (AP) and may play an important integrative role in the regulation of hormone production and pituitary feedback regulatory mechanisms (Köhrle 1996, 1999, Köhrle et al 1995, Braverman 1994. It is known that D1 is modulated by cytokines but the reports are controversial depending on species, method of cytokine application and organs concerned (Ozawa et al 1988, Pang et al 1989, Tang et al 1995, Pekary et al 1994, Ongphiphadhanakul et al 1994, Davies et al 1997. Therefore, we examined the effects of interleukin-1 (IL-1 ), interleukin-6 (IL-6) and tumor necrosis factor (TNF ) on pituitary deiodinase activities in reaggregates of rat APs since maintenance of cell-cell communication and interaction is known to affect their functional and regulatory properties in comparison to monolayer cultures , Rawlings & Hezareh 1996.…”

Section: Introductionmentioning

confidence: 99%

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Effects of proinflammatory cytokines on anterior pituitary 5'-deiodinase type I and type II

Baur¹,

Bauer²,

Jarry³

et al. 2000

Journal of Endocrinology

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Cytokines are locally produced in the anterior pituitary and act through para-/autocrine mechanisms to modulate cell growth and hormone production. 5 -Deiodinases type I (D1) and type II (D2) are also expressed in the anterior pituitary and play an integrative role in the regulation of hormone production and pituitary feedback. D1 activity is known to be regulated by proinflammatory cytokines in liver and thyroid. Therefore, we examined the effects of IL-1 , IL-6 and TNF on 5 -deiodinase activities in reaggregates of rat anterior pituitaries and rat somatomammotroph GH3 cells cultured alone, or in a bicameral culture system together with the murine folliculo-stellate (FS) cell line TtT/Gf. In reaggregate cultures of rat anterior pituitaries IL-1 stimulated D1 and D2 dosedependently and D2 activity was increased by TNF . When GH3 cells were cocultured with TtT/Gf cells, D2 activities were 2·3-fold lower than in GH3 cells cultured alone. TNF (50 ng/ml) and IL-6 (100 U/ml) stimulated D2 in GH3 cells when the cells were cultured alone and treated with these cytokines for 24 h. When TtT/Gf cells in the coculture model were treated with IL-1 , TNF and IL-6, no effect on D1 or D2 activities in GH3 cells was observed.In male, adult rats a single LPS injection (i.p.) stimulated D2 and D1 activities in the anterior pituitary, and decreased liver D1 activities and serum TSH levels. In vitro, LPS stimulation of the coculture model of GH3 and FS cells also increased D1 activity.Electrophoretic mobility shift assays (EMSAs) revealed that IL-1 and TNF activate the transcription factor NF B in reaggregates of rat anterior pituitaries and in TtT/Gf cells cultured alone or cocultured with GH3 cells. Taken together, these findings imply that in anterior pituitary cells 5 -deiodinase activities are stimulated by locally produced cytokines in a para-/autocrine manner but cell types other than FS cells seem to mediate some of the effects.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Effects of proinflammatory cytokines on anterior pituitary 5'-deiodinase type I and type II

Baur¹,

Bauer²,

Jarry³

et al. 2000

Journal of Endocrinology

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“…This clearly implicates that the low thyroid hormone levels are a consequence of the underlying condition and not of the low selenium level. Therefore, the influence of cytokines like interleukin-1, tumour necrosis factor or interferon, and glucocorticoids or drugs -and not the influence of diminished selenium levels -on 5 0 -deiodinase type I or II activity might be responsible for the low T3 levels in patients with severe sepsis (40,41). All drugs including low-dose dopamine or hydrocortisone, however, were used in a similar way in both groups of patients.…”

Section: Discussionmentioning

confidence: 99%

Selenium substitution has no direct effect on thyroid hormone metabolism in critically ill patients

Angstwurm

Schopohl

Gaertner

2004

European Journal of Endocrinology

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Background: In severe illness, plasma selenium levels are decreased; a decreased activity of the selenoenzyme 5 0 -deiodinase has been hypothesized to contribute to low tri-iodothyronine (T3) levels in non-thyroidal illness (NTI) syndrome in these patients. Objective: To analyse the influence of selenium substitution on thyroid hormone metabolism in patients with severe sepsis. Design: A prospective, randomized, controlled study at the medical internal intensive care unit of the University of Munich. Results are for 41 consecutive patients with severe sepsis with an APACHE II score . 15. Patients received either sodium selenite (500 mg/day for the first 3 days, reducing to 250 and then 125 mg/day every 3 days) or a placebo. Results: At study entry, APACHE II score and demographics were identical in both groups. The mean levels of TSH, free tri-iodithyronine and total T3, as well as plasma selenium and selenium-dependent peroxidase (GSH-Px) activity, were decreased. Plasma selenium and GSH-Px activity were normalized on days 3, 7 and 14 in patients receiving selenium (n ¼ 21), but remained below normal in the control patients. Patients receiving selenium had a better clinical outcome and thyroid hormone levels normalized earlier. Thyroid hormone levels increased in patients who showed clinical improvement, independent of selenium levels or selenium substitution. Conclusions: Selenium substitution in patients with NTI improves morbidity, but has no direct effect on the free and total thyroid hormones. In severely ill patients, decreased deiodinase activity due to low plasma selenium levels seems unlikely. After clinical revival, TSH and then the thyroidal hormones normalize independently of selenium substitution.

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“…It has been shown previously that TNF inhibits FRTL-5 iodide uptake in vitro (Pang et al 1993), whereas prolonged administration of TNF to mice produced a dosedependent decrease in concentrations of tri-iodothyronine (T 3 ), thyroxine and recombinant T 3 (Ozawa et al 1988). Administration of TNF to healthy volunteers induces changes in TSH and thyroid hormones resembling those found in non-thyroidal illness (NTI), suggesting involvement of TNF in NTI, in patients with infections or malignancy, in whom production of TNF is a feature (Van der Poll et al 1990).…”

Section: Discussionmentioning

confidence: 99%

The sodium iodide symporter gene and its regulation by cytokines found in autoimmunity

Ajjan

Watson²,

Findlay³

et al. 1998

Journal of Endocrinology

104

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Iodide concentration by the thyroid gland, an essential step for thyroid hormone synthesis, is mediated by the Na + /I symporter (NIS). To identify factors that may regulate this process, we have studied NIS gene expression in the Fisher rat thyroid cell line (FRTL-5) by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) technique. Increasing concentrations of bovine TSH (0·1, 1, 10, 50 and 100 mU/l), with or without tumour necrosis factor-(TNF ), interferon-(IFN ) or interleukin-1 (IL-1 ) were added to FRTL-5 cells previously deprived of TSH for a minimum of 5 days. RNA was extracted and samples were studied for NIS expression. TSH enhanced NIS mRNA expression in a dose-dependent manner, with induction evident at 0·1 mU/l, reaching a peak at 50 mU/l, an effect detected after 6 h of stimulation, but not in the first 2 h. Both TNF and, to a lesser extent, IL-1 inhibited basal and TSH-induced NIS expression. High concentrations of IFN also downregulated TSH-stimulated NIS mRNA expression.Using the same technique, we also investigated NIS mRNA tissue distribution in two male and one female Wistar rats. High levels of NIS expression were detected in the thyroid, stomach, and mammary gland, lower levels were found in the intestine, adipose tissue and liver, borderline levels were expressed in the salivary gland, and no expression was detected in the kidneys.In summary, we have shown that TSH upregulates rat NIS gene expression in vitro, and this induction can be modulated by cytokines. Analysis of the distribution of rat NIS mRNA ex vivo demonstrated variable levels of NIS transcription in different tissue samples.

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Effects of Tumor Necrosis Factor-α/Cachectin on Thyroid Hormone Metabolism in Mice*

Cited by 111 publications

References 29 publications

Effects of proinflammatory cytokines on anterior pituitary 5'-deiodinase type I and type II

Effects of proinflammatory cytokines on anterior pituitary 5'-deiodinase type I and type II

Selenium substitution has no direct effect on thyroid hormone metabolism in critically ill patients

The sodium iodide symporter gene and its regulation by cytokines found in autoimmunity

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