Effects of 5,5′-diphenylhydantoin on the thyroid status in rats

1996 ◽  
Vol 134 (2) ◽  
pp. 221-224 ◽  
Author(s):  
JP Schröder-van der Elst ◽  
D van der Heide ◽  
C van der Bent ◽  
E Kaptein ◽  
TJ Visser ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Metabolic Diseases ◽  
University Hospital ◽  
Pituitary Hormone ◽  
Type I ◽  
Uridine Diphosphate ◽  
Type Ii ◽  
Thyroid Status ◽  
Iodothyronine Deiodinase ◽  
Total Body Oxygen

Schröder-van der Elst JP, van der Heide D, van der Bent C, Kaptein E, Visser TJ, DiStefano JJ, Effects of 5,5′diphenylhydantoin on the thyroid status in rats. Eur J Endocrinol 1996;134:221–4. ISSN 0804–4643 Treatment of rats with phenytoin (DPH), an anti-epileptic drug, results in lower tissue thyroid hormone (TH) levels. To investigate if this is accompanied by tissue hypothyroidism, rats were treated for 3 weeks with DPH (50 mg/kg body wt in food). Thyroid hormone-dependent parameters were measured, and the results were compared to those of control rats and to those of athyreotic rats substituted with thyroxine + triiodothyronine (Tx + TH) to reach the same plasma TH levels as DPH-treated rats. These rats were mildly hypothyroid with regard to their TH and TSH levels and TH-dependent parameters. Both DPH and Tx + TH led to a decrease in plasma thyroxine (T4) and triiodothyronine (T3) (±70% of the control). The percentage free T4 was unchanged. Plasma thyrotropin (TSH) was increased only in the Tx + TH rats (sixfold). For DPH rats, pituitary hormone content was not different from the control; growth hormone was lower and TSH was higher in Tx + TH rats. In DPH and Tx + TH rats, an increase in hepatic T4 and T3 uridine-diphosphate glucuronyltransferase activity was found, likewise indicating a change in the metabolic pathway of TH. Hepatic iodothyronine deiodinase (ID) type I activity decreased in Tx + TH rats but did not alter in DPH rats. Hepatic α-glycerophosphate dehydrogenase (α-GPD) decreased in DPH and Tx + TH rats. Malic enzyme in liver was enhanced in DPH rats. In the brains of DPH rats the level of α-GPD activity was raised; in Tx + TH it was lowered. The ID type II activity in the brain was reduced in DPH rats, but ID type III did not change for either group. Total body oxygen consumption increased in DPH rats (13%); it decreased in Tx + TH rats (9%). Our results show that DPH causes changes comparable to mild hypothyroidism. The lack of or a diminished hypothyroid response can be explained as the attenuating agonistic effect of DPH, which is supported by O2 consumption, brain ID type II and α-GPD activities. The T4 content was reduced by 30% in thyroid digests; this, together with a reduced T4 secretion, can lead to serious hypothyroxinemia during prolonged DPH treatment. JP Schröder-van der Elst, Department of Metabolic Diseases and Endocrinology, Building 1, C4-R, University Hospital, Rijnsburgerweg 10, 2300 RC Leiden, The Netherlands

scholarly journals The Type II Deiodinase Is Retrotranslocated to the Cytoplasm and Proteasomes via p97/Atx3 Complex

2013 ◽  
Vol 27 (12) ◽  
pp. 2105-2115 ◽  
Author(s):  
Rafael Arrojo e Drigo ◽  
Péter Egri ◽  
Sungro Jo ◽  
Balázs Gereben ◽  
Antonio C. Bianco
Keyword(s):  
Molecular Weight ◽  
Endoplasmic Reticulum ◽  
Thyroid Hormone ◽  
High Molecular Weight ◽  
20S Proteasome ◽  
Type I ◽  
Type Ii ◽  
Cell Models ◽  
Natural Substrate ◽  
Iodothyronine Deiodinase

The type II iodothyronine deiodinase (D2) is a type I endoplasmic reticulum (ER)-resident thioredoxin fold-containing selenoprotein that activates thyroid hormone. D2 is inactivated by ER-associated ubiquitination and can be reactivated by two ubiquitin-specific peptidase-class D2-interacting deubiquitinases (DUBs). Here, we used D2-expressing cell models to define that D2 ubiquitination (UbD2) occurs via K48-linked ubiquitin chains and that exposure to its natural substrate, T4, accelerates UbD2 formation and retrotranslocation to the cytoplasm via interaction with the p97-ATPase complex. D2 retrotranslocation also includes deubiquitination by the p97-associated DUB Ataxin-3 (Atx3). Inhibiting Atx3 with eeyarestatin-I did not affect D2:p97 binding but decreased UbD2 retrotranslocation and caused ER accumulation of high-molecular weight UbD2 bands possibly by interfering with the D2-ubiquitin-specific peptidases binding. Once in the cytosol, D2 is delivered to the proteasomes as evidenced by coprecipitation with 19S proteasome subunit S5a and increased colocalization with the 20S proteasome. We conclude that interaction between UbD2 and p97/Atx3 mediates retranslocation of UbD2 to the cytoplasm for terminal degradation in the proteasomes, a pathway that is accelerated by exposure to T4.

scholarly journals Inhibition of type I and type II iodothyronine deiodinase activity in rat liver, kidney and brain produced by selenium deficiency

1989 ◽  
Vol 259 (3) ◽  
pp. 887-892 ◽  
Author(s):  
G J Beckett ◽  
D A MacDougall ◽  
F Nicol ◽  
J R Arthur
Keyword(s):  
Body Weight ◽  
Thyroid Hormone ◽  
Feedback Inhibition ◽  
Selenium Deficiency ◽  
Stress Factors ◽  
Type I ◽  
Type Ii ◽  
Hormone Metabolism ◽  
Iodothyronine Deiodinase ◽  
Thyroid Hormone Metabolism

Selenium deficiency for periods of 5 or 6 weeks in rats produced an inhibition of tri-iodothyronine (T3) production from added thyroxine (T4) in brain, liver and kidney homogenate. This inhibition was reflected in plasma T4 and T3 concentrations, which were respectively increased and decreased in selenium-deficient animals. Although plasma T4 levels increased in selenium-deficient animals, this did not produce the normal feedback inhibition on thyrotropin release from the pituitary. Selenium deficiency was confirmed in the animals by decreased selenium-dependent glutathione peroxidase (Se-GSH-Px) activity in all of these tissues. Administration of selenium, as a single intraperitoneal injection of 200 micrograms of selenium (as Na2SeO3)/kg body weight completely reversed the effects of selenium deficiency on thyroid-hormone metabolism and partly restored the activity of Se-GSH-Px. Selenium administration at 10 micrograms/kg body weight had no significant effect on thyroid-hormone metabolism or on Se-GSH-Px activity in any of the tissues studied. The characteristic changes in plasma thyroid-hormone levels that occurred in selenium deficiency appeared not to be due to non-specific stress factors, since food restriction to 75% of normal intake or vitamin E deficiency produced no significant changes in plasma T4 or T3 concentration. These data are consistent with the view that the Type I and Type II iodothyronine deiodinase enzymes are seleno-enzymes or require selenium-containing cofactors for activity.

Regulation of Mammary Gland Sensitivity to Thyroid Hormones During the Transition from Pregnancy to Lactation

2008 ◽  
Vol 233 (10) ◽  
pp. 1309-1314 ◽  
Author(s):  
A. V. Capuco ◽  
E. E. Connor ◽  
D. L. Wood
Keyword(s):  
Mammary Gland ◽  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Thyroid Hormone Receptor ◽  
Physiological State ◽  
Expression Patterns ◽  
Type I ◽  
Hormone Activity ◽  
Iodothyronine Deiodinase ◽  
Copy Numbers

Thyroid hormones are galactopoietic and help to establish the mammary gland’s metabolic priority during lactation. Expression patterns for genes that can alter tissue sensitivity to thyroid hormones and thyroid hormone activity were evaluated in the mammary gland and liver of cows at 53, 35, 20, and 7 days before expected parturition, and 14 and 90 days into the subsequent lactation. Transcript abundance for the three isoforms of iodothyronine deiodinase, type I ( DIO1), type II ( DIO2) and type III ( DIO3), thyroid hormone receptors alpha1 ( TRα 1), alpha2 ( TRα 2) and beta1 ( TRβ 1), and retinoic acid receptors alpha ( RXRα) and gamma ( RXRγ), which act as coregulators of thyroid hormone receptor action, were evaluated by quantitative RT-PCR. The DIO3 is a 5-deiodinase that produces inactive iodothyronine metabolites, whereas DIO1 and DIO2 generate the active thyroid hormone, triiodothyronine, from the relatively inactive precursor, thyroxine. Low copy numbers of DIO3 transcripts were present in mammary gland and liver. DIO2 was the predominant isoform expressed in mammary gland and DIO1 was the predominant isoform expressed in liver. Quantity of DIO1 mRNA in liver tissues did not differ with physiological state, but tended to be lowest during lactation. Quantity of DIO2 mRNA in mammary gland increased during lactation ( P < 0.05), with copy numbers at 90 days of lactation 6-fold greater than at 35 and 20 days prepartum. When ratios of DIO2/DIO3 mRNA were evaluated, the increase was more pronounced (>100-fold). Quantity of TRβ 1 mRNA in mammary gland increased with onset of lactation, whereas TRα 1 and TRα 2 transcripts did not vary with physiological state. Conversely, quantity of RXRα mRNA decreased during late gestation to low levels during early lactation. Data suggest that increased expression of mammary TRβ 1 and DIO2, and decreased RXRα, provide a mechanism to increase thyroid hormone activity within the mammary gland during lactation.

Differential subcellular distribution of rat prostatic steroid 5α-reductase isozyme activities

1996 ◽  
Vol 134 (3) ◽  
pp. 386-392 ◽  
Author(s):  
Paul N Span ◽  
CGJ Sweep ◽  
Theo J Benraad ◽  
Anthony GH Smals
Keyword(s):  
Nuclear Localization ◽  
Subcellular Distribution ◽  
Subcellular Fractions ◽  
University Hospital ◽  
Type I ◽  
Target Tissue ◽  
Type Ii ◽  
Rat Prostate ◽  
Isozyme Activity

Span PN, Sweep CGJ, Benraad TJ, Smals AGH. Differential subcellular distribution of rat prostatic steroid 5α-reductase isozyme activities. Eur J Endocrinol 1996;134:386–92. ISSN 0804–4643 The rat prostate, a classical androgen-target tissue, contains both known isozymes of steroid 5α-reductase, i.e. type I and type II. So far, the role of the type I isozyme has been proposed as catabolic. The abundant expression of type I 5α-reductase in an androgen-target tissue is therefore puzzling. Assessment of the subcellular localization of 5α-reductase isozymes in rat prostate might contribute in elucidating their possibly distinct roles. After obtaining crude subcellular fractions by differential centrifugation, both isozyme activities were measured at neutral pH by plotting according to Eadie–Scatchard. The observations were extended by assessment of pH-dependent velocity ratios and type II 5α-reductase inhibitor sensitivities in these subcellular fractions. The results indicated a preferentially—although not exclusively—nuclear localization for the type I and a predominantly microsomal localization for the type II isozyme activity in the rat prostate. In conclusion, the nuclear localization of the type I isozyme seems not to concur with its proposed catabolic role. AGH Smals, Department of Medicine, Division of Endocrinology, University Hospital Nijmegen, Geert Grooteplein Zuid 8, 6525 GA Nijmegen, The Netherlands

scholarly journals Characterization of Human Iodothyronine Sulfotransferases1

1999 ◽  
Vol 84 (4) ◽  
pp. 1357-1364 ◽  
Author(s):  
Monique H. A. Kester ◽  
Ellen Kaptein ◽  
Thirza J. Roest ◽  
Caren H. van Dijk ◽  
Dick Tibboel ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Human Liver ◽  
Type I ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Iodothyronine Deiodinase ◽  
Liver Cytosol ◽  
Thyroid Hormone Metabolism ◽  
Liver And Kidney ◽  
Phenol Sulfotransferase

Sulfation is an important pathway of thyroid hormone metabolism that facilitates the degradation of the hormone by the type I iodothyronine deiodinase, but little is known about which human sulfotransferase isoenzymes are involved. We have investigated the sulfation of the prohormone T4, the active hormone T3, and the metabolites rT3 and 3,3′-diiodothyronine (3,3′-T2) by human liver and kidney cytosol as well as by recombinant human SULT1A1 and SULT1A3, previously known as phenol-preferring and monoamine-preferring phenol sulfotransferase, respectively. In all cases, the substrate preference was 3,3′-T2 &gt;&gt; rT3 &gt; T3 &gt; T4. The apparent Km values of 3,3′-T2 and T3 [at 50 μmol/L 3′-phosphoadenosine-5′-phosphosulfate (PAPS)] were 1.02 and 54.9μ mol/L for liver cytosol, 0.64 and 27.8 μmol/L for kidney cytosol, 0.14 and 29.1 μmol/L for SULT1A1, and 33 and 112 μmol/L for SULT1A3, respectively. The apparent Km of PAPS (at 0.1μ mol/L 3,3′-T2) was 6.0 μmol/L for liver cytosol, 9.0μ mol/L for kidney cytosol, 0.65 μmol/L for SULT1A1, and 2.7μ mol/L for SULT1A3. The sulfation of 3,3′-T2 was inhibited by the other iodothyronines in a concentration-dependent manner. The inhibition profiles of the 3,3′-T2 sulfotransferase activities of liver and kidney cytosol obtained by addition of 10 μmol/L of the various analogs were better correlated with the inhibition profile of SULT1A1 than with that of SULT1A3. These results indicate similar substrate specificities for iodothyronine sulfation by native human liver and kidney sulfotransferases and recombinant SULT1A1 and SULT1A3. Of the latter, SULT1A1 clearly shows the highest affinity for both iodothyronines and PAPS, but it remains to be established whether it is the prominent isoenzyme for sulfation of thyroid hormone in human liver and kidney.

scholarly journals Type II iodothyronine deiodinase protein in chicken choroid plexus: additional perspectives on T3 supply in the avian brain

2004 ◽  
Vol 183 (1) ◽  
pp. 235-241 ◽  
Author(s):  
C H J Verhoelst ◽  
V M Darras ◽  
S A Roelens ◽  
G M Artykbaeva ◽  
S Van der Geyten
Keyword(s):  
Epithelial Cells ◽  
Choroid Plexus ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Type I ◽  
Mrna Levels ◽  
Type Ii ◽  
Iodothyronine Deiodinase ◽  
Blood Brain ◽  
D2 Protein

It is widely accepted that type II iodothyronine deiodinase (D2) is mostly present in the brain, where it maintains the homeostasis of thyroid hormone (TH) levels. Although intensive studies have been performed on activity and mRNA levels of the deiodinases, very little is known about their expression at the protein level due to the lack of specific antisera. The current study reports the production of a specific D2 polyclonal antiserum and its use in the comparison of D2 protein distribution with that of type I (D1) and type III (D3) deiodinase protein in the choroid plexus at the blood–brain barrier level. Immunocytochemistry showed very high D2 protein expression in the choroid plexus, especially in the epithelial cells, whereas the D1 and D3 proteins were absent. Furthermore, dexamethasone treatment led to an up-regulation of the D2 protein in the choroid plexus. The expression of D2 protein in the choroid plexus led to a novel insight into the working mechanism of the uptake and transport of thyroid hormones along the blood–brain barrier in birds. It is hypothesized that D2 allows the prohormone thyroxine (T4) to be converted into the active 3,5,3′-triiodothyronine (T3). Within the choroidal epithelial cells. T3 is subsequently bound to its carrier protein, transthyretin (TTR), to allow transport through the cerebrospinal fluid. Neurons can thus not only be provided with a sufficient T3 level via the aid of the astrocytes, as was hypothesized previously based on in situ hybridization data, but also by means of T4 deiodination by D2, directly at the blood–brain barrier level.

scholarly journals PERFORATED PEPTIC ULCERS: 3 YEAR EXPERIENCE IN KLAIPEDA UNIVERSITY HOSPITAL

2019 ◽  
Vol 29 (2) ◽  
pp. 39-43
Author(s):  
Šarūnas Dailidėnas ◽  
Martynas Garčauskis ◽  
Gintarė Srėbaliūtė ◽  
Jonas Jurgaitis ◽  
Paulius Žeromskas ◽  
...  
Keyword(s):  
Data Analysis ◽  
Perforated Peptic Ulcer ◽  
University Hospital ◽  
Type I ◽  
Open Approach ◽  
Peptic Ulcers ◽  
Type Ii ◽  
Average Hospital ◽  
Mannheim Peritonitis Index ◽  
The Mean

Perforation is second most common complication of peptic ulcers with mortality rate ranging from 3 to 30 %. For best outcomes this condition must be diagnosed and managed as soon as possible. Objectives and methods. The aim of this study was to present our clinical experience in managing perforated peptic ulcers. Retrospective data analysis of patients treated for perforated peptic ulcers from year 2015 to 2017 was performed. Statistical data analysis was carried out using the SPSS 20.0 software. Results. 90 patients were treated for perforated peptic ulcers. The female and male ratio was 1:1.25 with the mean patient age of 61.60±19.42 years. There were no more data from 16 patients. The average hospital stay was 12.89±13.31 days. 11% of the patients had type I, 49% – type II, 24% – type III, 5%- type IV, 11% – type V ulcer according to modified Johnson classification. 91% underwent ulcerorrhaphy, 4% -Billroth type I surgery, 2% – Billroth type II surgery and 1% had atypic resection. 84% of surgeries were performed with laparotomic approach, 12% – laparos-copically, 4% had a conversion. The mean duration of the operation was 85.2±4.64 minutes. The average Mannheim Peritonitis Index between the patients was 17.135±7.36. 24% of patients with perforated peptic ulcer died. Statistically significant correlation was observed between the Mannheim Peritonitis Index and mortality (r=0.640; p&lt;0.05), age and mortality (r=0.459; p&lt;0.05) and between age and Mannheim Peritonitis Index (r=0.740; p&lt;0.05). Conclusion. During the period from 2015 to 2017 90 patients were treated for PPU. Half of the patients had type II ulcer localization according to modified Johnson classification. Simple closure was performed for 91% of the patients, 84% of all surgeries were performed with an open approach. Statistically significant correlation was found between Mannheim Peritonitis Index and mortality, age and mortality and between age and Mannheim Peritonitis Index. No significant correlation was observed between the approach and the outcome. There could be a bigger role in laparascopic surgery treating PPU. It is important for clinicists to consider about PPI for treatment when prescribing NSAIDs, especially in elderly and hospitalized patients in order to avoid peptic ulcers and its complications.

scholarly journals Effects of concomitant selenium and vitamin E administration on thyroid hormone metabolism in broilers

2018 ◽  
Vol 68 (3) ◽  
pp. 355
Author(s):  
A. C. PAPPAS ◽  
B. M. KOTSAMPASI ◽  
K. KALAMARAS ◽  
K. FEGEROS ◽  
G. ZERVAS ◽  
...  
Keyword(s):  
Vitamin E ◽  
Thyroid Hormone ◽  
Control Diet ◽  
Dietary Treatment ◽  
Tocopheryl Acetate ◽  
Type I ◽  
Hormone Metabolism ◽  
Iodothyronine Deiodinase ◽  
Thyroid Hormone Metabolism ◽  
Diet Control

A total of 400, as hatched, broilers were used to investigate the effect of selenium (Se) and vitamin E supplementation on thyroid hormones metabolism. There were 5 replicates of 4 dietary treatments namely: control (C), a soybean meal maize basal diet with adequate Se and vitamin E (0.3 mg Se per kg diet and 80 mg vitamin E per kg diet), control diet with Se added (Se+, with an additional 1 mg of Se per kg of diet), control diet with vitamin E added (E+, with an additional 350 mg of vitamin E per kg of diet) and Se+E+ (with additional 1 mg of Se and 350 mg of vitamin E per kg of diet). Diets were isonitrogenous and isocaloric. Zinc L-selenomethionine complex was used to increase Se content and dl-α-tocopheryl acetate to increase vitamin E content. The experiment lasted 42 days. Plasma Se concentration increased in Se+ groups, while whole blood glutathione peroxidase (GPx) activity increased in Se+, E+ and Se+E+ groups compared to control. Hepatic type I iodothyronine deiodinase (ID-I) and thyroid hormone concentrations were unaffected by any dietary treatment. It is concluded that supplementation with Se or vitamin Ε alone or in combination above animal’s requirements does not affect thyroid hormone metabolism and liver ID-I activity under the conditions examined.

scholarly journals Iodothyronine deiodinases and the control of plasma and tissue thyroid hormone levels in hyperthyroid tilapia (Oreochromis niloticus)

2005 ◽  
Vol 184 (3) ◽  
pp. 467-479 ◽  
Author(s):  
S Van der Geyten ◽  
N Byamungu ◽  
G E Reyns ◽  
E R Kühn ◽  
V M Darras
Keyword(s):  
Thyroid Hormone ◽  
Oreochromis Niloticus ◽  
Degradation Mechanism ◽  
Current Data ◽  
Type I ◽  
Iodothyronine Deiodinase ◽  
Hormone Levels ◽  
Thyroid Hormone Levels

Thyroid status is one of the most potent regulators of peripheral thyroid hormone metabolism in vertebrates. Despite this, the few papers that have been published concerning the role of thyroid hormones in the regulation of thyroid function in fish often offer conflicting data. We therefore set out to investigate the effects of tetraiodothyronine (thyroxine) (T4) or tri-iodothyronine (T3) supplementation (48 p.p.m.) via the food on plasma and tissue thyroid hormone levels as well as iodothyronine deiodinase (D) activities in the Nile tilapia (Oreochromis niloticus). T4 supplementation did not induce a hyperthyroid state and subsequently had no effects on the thyroid hormone parameters measured, with the liver as the sole notable exception. In T4-fed tilapias, the hepatic T4 levels increased substantially, and this was accompanied by an increase in in vitro type I deiodinase (D1) activity. Although the lack of effect of T4 supplementation could be partially explained by an inefficient uptake of T4 from the gut, our current data suggest that also the increased conversion of T4 into reverse (r)T3 by the D1 present in the liver plays an important role in this respect. In addition, T3 supplementation increased plasma T3 and decreased plasma T4 concentrations. T3 levels were also increased in the liver, brain, kidney, gill and white muscle, but without affecting local T4 concentrations. However, this increase in T3 availability remained without effect on D1 activity in liver and kidney. This observation, together with the 6-n-propylthiouracyl (PTU) insensitivity of the D1 enzyme in fish, sets the D1 in teleost fish clearly apart from its mammalian and avian counterparts. The changes in hepatic deiodinases confirm the role of the liver as an important T3-regulating tissue. However, the very short plasma half-life of exogenously administered T3 implies the existence of an efficient T3 clearing/degradation mechanism other than deiodination.

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