scholarly journals Effect of selenium deficiency on hepatic type I 5-iodothyronine deiodinase activity and hepatic thyroid hormone levels in the rat

1992 ◽  
Vol 282 (2) ◽  
pp. 483-486 ◽  
Author(s):  
G J Beckett ◽  
A Russell ◽  
F Nicol ◽  
P Sahu ◽  
C R Wolf ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Selenium Deficiency ◽  
Type I ◽  
Hepatic Enzymes ◽  
Glutathione S Transferase ◽  
Iodothyronine Deiodinase ◽  
Hepatic Glutathione ◽  
Liver Homogenates ◽  
Thyroid Hormone Levels ◽  
Gst Activity

Selenium deficiency in rats for a period of up to 6 weeks inhibited both the production of 3,3′, 5-tri-iodothyronine (T3) from thyroxine (T4) (5′-deiodination) and also the catabolism of T3 to 3,3′-di-iodothyronine (5-deiodination) in liver homogenates. The hepatic stores of T3 were decreased by only 8% in selenium deficiency, despite the T3 production rate from T4 being only 7% of the rate found in selenium-supplemented rats. Hepatic glutathione S-transferase (GST) activity was increased in both hypothyroidism and selenium deficiency, but apparently by different mechanisms, since mRNA expression for this family of enzymes was lowered by hypothyroidism and increased in selenium deficiency. It is concluded that, since both T3 production and catabolism are inhibited by selenium deficiency, there is little change in hepatic T3 stores, and therefore the changes in the activity of certain hepatic enzymes, such as GST, that are found in selenium deficiency are not the result of tissue hypothyroidism.

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.

scholarly journals The changes in hepatic enzyme expression caused by selenium deficiency and hypothyroidism in rats are produced by independent mechanisms

1990 ◽  
Vol 266 (3) ◽  
pp. 743-747 ◽  
Author(s):  
G J Beckett ◽  
F Nicol ◽  
D Proudfoot ◽  
K Dyson ◽  
G Loucaides ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Malic Enzyme ◽  
Selenium Deficiency ◽  
Hepatic Enzyme ◽  
Enzyme Expression ◽  
Glutathione S Transferase ◽  
Plasma Enzymes ◽  
Glycerophosphate Dehydrogenase ◽  
Se Deficiency ◽  
Gst Activity

Selenium (Se) deficiency for 5 weeks in rats produced changes in the activity of a number of hepatic, renal and plasma enzymes. In animals whose food intake was restricted to 75% of normal for 2 weeks, Se deficiency produced significant increases in the activity of hepatic cytosolic ‘malic’ enzyme and mitochondrial alpha-glycerophosphate dehydrogenase (GPD), two enzymes that are particular sensitive to the thyroid-hormone concentrations in tissue. Propylthiouracil-induced hypothyroidism produced significant decreases in ‘malic’ enzyme and GPD activities. The effect of hypothyroidism on the activity of ‘malic’ enzyme, GPD and other enzymes studied in liver and plasma was often opposite to that seen in Se deficiency. Glutathione S-transferase (GST) activity was increased by both Se deficiency and hypothyroidism, but in hypothyroid animals further significant increases in GST were produced by Se deficiency. These data suggest that the changes in enzyme expression observed in Se deficiency are not caused by decreased tissue exposure to thyroid hormones.

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.

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 The effects of selenium deficiency on hepatic type-I iodothyronine deiodinase and protein disulphide-isomerase assessed by activity measurements and affinity labelling

1991 ◽  
Vol 274 (1) ◽  
pp. 297-300 ◽  
Author(s):  
J R Arthur ◽  
F Nicol ◽  
E Grant ◽  
G J Beckett
Keyword(s):  
Selenium Deficiency ◽  
Protein Band ◽  
Major Protein ◽  
Type I ◽  
Iodothyronine Deiodinase ◽  
Protein Disulphide Isomerase ◽  
Activity Measurements ◽  
Fold Stimulation

We determined protein disulphide-isomerase (PDI) and iodothyronine deiodinase (ID-I) activities in liver homogenates from rats subjected to selenium (Se) and/or iodine deficiencies and food restriction. Additionally, the effects of propylthiouracil (PTU) on the enzymes were studied in vivo and in vitro. Selenium deficiency markedly inhibited ID-I activity, but had no significant effects on PDI. Iodine deficiency resulted in a 1.6-fold stimulation in ID-I and a 1.2-fold stimulation in PDI activities. ID-I was much more sensitive than PDI to the inhibitory effects of PTU both in vitro and in vivo. By using a 3,3′,5′-tri[125I]iodothyronine affinity label, two major protein bands were identified when hepatic microsomal fractions from Se-sufficient rats were subjected to SDS/PAGE and autoradiography. These bands had molecular masses of 55 and 27.5 kDa, which are similar to those of PDI and ID-I respectively. Selenium deficiency resulted in the loss of the 27.5 kDa band, but did not affect the intensity of the 55 kDa band. These results are consistent with the changes in PDI and ID-I enzyme activities. Previous studies have shown that 75Se may be incorporated in vivo into the 27.5 kDa protein band. This, taken together with our observation that Se is required for the expression of ID-I and the 27.5 kDa protein band, strongly suggests that ID-I is a selenoprotein.

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.

The role of selenium in thyroid hormone metabolism

1991 ◽  
Vol 69 (11) ◽  
pp. 1648-1652 ◽  
Author(s):  
John R. Arthur
Keyword(s):  
Thyroid Hormone ◽  
Iodine Deficiency ◽  
Selenium Deficiency ◽  
Major Influence ◽  
Type I ◽  
Hormone Metabolism ◽  
Thyroid Hormone Metabolism ◽  
Iodothyronine Deiodinases ◽  
Clinical Changes

In animals, decreases in selenium-containing glutathione peroxidase activity and the resultant impairment of peroxide metabolism can account for many, but not all of the biochemical and clinical changes caused by selenium deficiency. Recently, however, type I iodothyronine 5′-deiodinase has also been shown to be a selenium-containing enzyme. This explains the impairment of thyroid hormone metabolism caused by selenium deficiency in animals with a normal vitamin E status. Since iodothyronine 5′-deiodinases are essential for the production of the active thyroid hormone 3,5,3′-triiodothyronine, some of the consequences of selenium deficiency may result from thyroid changes rather than inability to metabolise peroxides. In particular, the impaired thyroid hormone metabolism may be responsible for decreased growth and resistance to cold stress in selenium-deficient animals. A further consequence of the role of selenium in thyroid hormone metabolism is the exacerbation of some of the thyroid changes in iodine deficiency by a concurrent selenium deficiency. Selenium status may therefore have a major influence on the outcome of iodine deficiency in both human and animal populations.Key words: selenium, thyroid hormones, iodothyronine deiodinases, iodine, nutritional disorders.

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.

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