scholarly journals Activities of UDP-glucuronyltransferase, beta-glucuronidase and deiodinase types I and II in hyper- and hypothyroid rats

2004 ◽  
Vol 181 (3) ◽  
pp. 393-400 ◽  
Author(s):  
SM van der Heide ◽  
BJ Joosten ◽  
ME Everts ◽  
PH Klaren
Keyword(s):  
Specific Activity ◽  
Rat Kidney ◽  
Type I ◽  
Hormone Metabolism ◽  
Thyroid Status ◽  
Adult Rats ◽  
Iodothyronine Deiodinase ◽  
Thyroid Hormone Metabolism ◽  
Glucuronidase Activity ◽  
Liver And Kidney

We have investigated the hypothesis that uridine 5'-diphosphate (UDP)-glucuronyltransferases (UGTs) and beta-glucuronidase are jointly involved in a mechanism for the storage and mobilization of iodothyronine metabolites in liver, kidney, heart and brain. Specifically, we predicted UGT activities to decrease and increase respectively, and beta-glucuronidase activity to increase and decrease respectively in hypo- and hyperthyroidism. To this end we have studied the effects of thyroid status on the activities of different enzymes involved in thyroid hormone metabolism in liver, kidney, heart and brain from adult rats with experimentally induced hypo- and hyperthyroidism. We used whole organ homogenates to determine the specific enzyme activities of phenol- and androsteron-UGT, beta-glucuronidase, as well as iodothyronine deiodinase types I and II. Deiodinase type I activities in liver and kidney were decreased in hypothyroid animals and, in liver only, increased in hyperthyroidism. Deiodinase type II activity was increased in hyperthyroid rat kidney only. Interestingly, in the heart, deiodinase type I-specific activity was increased fourfold, although the increase was not statistically significant. Cardiac deiodinase type I activity was detectable but not sensitive to thyroid status. Hepatic phenol-UGT as well as androsteron-UGT activities were decreased in hypothyroid rats, with specific androsteron-UGT activities two to three orders of magnitude lower than phenol-UGT activities. Both UGT isozymes were well above detection limits in heart, but appeared to be insensitive to thyroid status. In contrast, cardiac beta-glucuronidase activity decreased in hypothyroid tissue, whereas the activity of this enzyme in the other organs investigated did not change significantly.In summary, cardiac beta-glucuronidase, albeit in low levels, and hepatic phenol-UGT activities were responsive only to experimental hypothyroidism. Although a high basal activity of the pleiotropic beta-glucuronidase masking subtle activity changes in response to thyroid status cannot be ruled out, we conclude that hepatic, renal and cardiac UGT and beta-glucuronidase activities are not regulated reciprocally with thyroid status.

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 >> rT3 > T3 > 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 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 Type 1 iodothyronine deiodinase in human physiology and disease

2011 ◽  
Vol 209 (3) ◽  
pp. 283-297 ◽  
Author(s):  
Ana Luiza Maia ◽  
Iuri Martin Goemann ◽  
Erika L Souza Meyer ◽  
Simone Magagnin Wajner
Keyword(s):  
Human Physiology ◽  
Thyroid Hormone ◽  
Active Form ◽  
Normal Function ◽  
Type I ◽  
Hormone Metabolism ◽  
Iodothyronine Deiodinase ◽  
Thyroid Hormone Metabolism ◽  
Iodothyronine Deiodinases

Thyroid hormone is essential for the normal function of virtually all tissues. The iodothyronine deiodinases catalyze the removal of an iodine residue from the pro-hormone thyroxine (T4) molecule, thus producing either the active form triiodothyronine (T3; activation) or inactive metabolites (reverse T3; inactivation). Type I deiodinase (D1) catalyzes both reactions. Over the last years, several studies have attempted to understand the mechanisms of D1 function, underlying its effects on normal thyroid hormone metabolism and pathological processes. Although peripheral D1-generated T3 production contributes to a portion of plasma T3 in euthyroid state, pathologically increased thyroidal D1 activity seems to be the main cause of the elevated T3 concentrations observed in hyperthyroid patients. On the other hand, D1-deficient mouse models show that, in the absence of D1, inactive and lesser iodothyronines are excreted in feces with the loss of associated iodine, demonstrating the scavenging function for D1 that might be particularly important in an iodine deficiency setting. Polymorphisms in the DIO1 gene have been associated with changes in serum thyroid hormone levels, whereas decreased D1 activity has been reported in the nonthyroid illness syndrome and in several human neoplasias. The current review aims at presenting an updated picture of the recent advances made in the biochemical and molecular properties of D1 as well as its role in human physiology.

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.

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 Thyroid hormone deiodination in the domestic cat

2000 ◽  
Vol 24 (1) ◽  
pp. 119-126 ◽  
Author(s):  
DJ Foster ◽  
KL Thoday ◽  
GJ Beckett
Keyword(s):  
Thyroid Hormone ◽  
Similar Rate ◽  
Domestic Cat ◽  
Type I ◽  
Iodothyronine Deiodinase ◽  
Physiological Conditions ◽  
Affinity Labelling ◽  
Liver And Kidney ◽  
Assay Conditions

We have investigated thyroid hormone deiodination in the liver, kidney and thyroid of the domestic cat. Affinity labelling with (125)I-bromoacetyl reverse T(3) (125)(I-BrAc-rT(3) demonstrated that liver and kidney, but not the thyroid, express type I iodothyronine deiodinase (IDI), results that were confirmed by measuring the activity of the IDI using (125)I-rT(3) and T(4) as substrate. Feline hepatic and renal IDI metabolised rT(3) at approximately 0.2% of the rate of rat hepatic IDI under identical assay conditions. The K(m) of the feline enzyme was at least 500-fold greater than that of rat IDI. However, feline and rat hepatic IDI metabolised T(4) at a similar rate and had similar K(m) values (1.35 microM and 2.25 microM, respectively). This study demonstrates that cats and rats express IDI in the liver and kidney in similar concentrations; however, the feline enzyme appears unable to utilise rT(3) as a substrate under physiological conditions.

Effects of thyroid status on brain catecholamine biosynthesis in adult rats: assessment by a steady-state method

1986 ◽  
Vol 111 (3) ◽  
pp. 383-389 ◽  
Author(s):  
P. E. Harris ◽  
C. Dieguez ◽  
B. M. Lewis ◽  
R. Hall ◽  
M. F. Scanlon
Keyword(s):  
Steady State ◽  
Specific Activity ◽  
Dopamine Synthesis ◽  
Mediobasal Hypothalamus ◽  
Thyroid Status ◽  
Adult Rats ◽  
Catecholamine Biosynthesis ◽  
Steady State Method ◽  
Catecholamine Turnover ◽  
State Method

ABSTRACT Effects of thyroid status on brain catecholamine turnover in adult rats were investigated using a steady-state method. Rats were treated for 3 weeks with s.c. injections of l-thyroxine (0·4 mg/kg), aminotriazole in drinking water (0·1%, w/v) or vehicle. After 2 weeks of treatment rats were implanted chronically with lateral intracerebroventricular (i.c.v.) cannulae. They were injected i.c.v. with [3H]tyrosine 1 week later. Catecholamine and tyrosine content and specific activity were measured in mediobasal hypothalamus, anterior hypothalamus and striatum, using high-performance liquid chromatography with electrochemical detection. Thyroxine treatment resulted in a significant increase in noradrenaline and dopamine synthesis localized to the mediobasal hypothalamus. Conversely, aminotriazole treatment resulted in a significant decrease in noradrenaline synthesis localized to the mediobasal hypothalamus. The localization of these changes in catecholamine turnover to the mediobasal hypothalamus suggests that they may be specific functional effects which are of importance in the overall integrated control of thyroid function. J. Endocr. (1986) 111, 383–389

scholarly journals Determinants of Iodothyronine Deiodinase Activities in Rodent Uterus

Endocrinology ◽  
2003 ◽  
Vol 144 (10) ◽  
pp. 4253-4261 ◽  
Author(s):  
Emily C. Wasco ◽  
Elena Martinez ◽  
Katherine S. Grant ◽  
Emily A. St. Germain ◽  
Donald L. St. Germain ◽  
...  
Keyword(s):  
Time Course ◽  
Female Rats ◽  
Ovariectomized Rats ◽  
Hormone Metabolism ◽  
Similar Time ◽  
Pregnant Rats ◽  
Iodothyronine Deiodinase ◽  
Thyroid Hormone Metabolism ◽  
Before And After ◽  
17Β Estradiol

The deiodinase types 2 and 3 (D2, D3), which convert T4 to active and inactive metabolites, respectively, are expressed in the rodent uterus and highly induced during pregnancy. To examine the factors regulating the expression of these enzymes in this tissue, we studied D2 and D3 activity in pregnant rats, in pseudopregnant rats before and after the induction of artificial decidualization, and in ovariectomized rats treated with 17β-estradiol (E2) and/or progesterone (P). Our results demonstrate that induction of D3 activity begins immediately after implantation and increases markedly over the next 72 h. A similar time course and magnitude of D3 induction is noted in the artificially decidualized uterus in pseudopregnant rats, whereas only minimal increases in activity are observed in the nondecidualized control uterine horns in the same animal. In contrast, D2 activity is not induced by a decidualization stimulus. In spontaneously cycling female rats, both D2 and D3 were observed to be 3- to 8-fold higher in proestrus, compared with diestrus. Furthermore, levels of D2 and D3 activity were greatly increased in ovariectomized rats given E2 and P in various combinations. D2 activity was stimulated primarily by E2, whereas E2 and P acted synergistically to increase D3 activity. These results demonstrate that E2 and P regulate thyroid hormone metabolism in the uterus, and that the implantation process is a potent stimulus for the induction of D3 activity in this organ. Such precise and profound changes in deiodinase expression are likely to play important physiological roles in fetal development and may influence uterine function.

scholarly journals Renal and hepatic distribution of type I and type III iodothyronine deiodinase protein in chicken

2004 ◽  
Vol 181 (1) ◽  
pp. 85-90 ◽  
Author(s):  
CH Verhoelst ◽  
S Van Der Geyten ◽  
VM Darras
Keyword(s):  
Cellular Localization ◽  
Circular Muscle ◽  
Immunocytochemical Staining ◽  
Transitional Epithelium ◽  
Type I ◽  
Zonal Distribution ◽  
Iodothyronine Deiodinase ◽  
Type Iii ◽  
Liver And Kidney

Iodothyronine deiodinase in vitro activity studies in the chicken showed the presence of type I and type III iodothyronine deiodinase activity in both liver and kidney. Due to the lack of a specific antiserum the cellular localization of the deiodinase proteins could not be revealed until now. In the present study, specific antisera were used to study the renal and hepatic distribution of type I and type III iodothyronine deiodinase protein in the chicken. Immunocytochemical staining of liver tissue led to an immunopositive signal in the hepatocytes in general. Moreover, a zonal distribution could be detected for both enzymes. Maximum protein expression was shown in a thin layer of hepatocytes bordering the blood veins. Although pericentral localization of type I deiodinase protein has been previously reported in the rat, no data were given concerning type III deiodinase protein. In the present study, we report the co-localization of both enzymes in the chicken. Co-expression of the deiodinases was also found in the kidney. Expression of both proteins was associated with the tubular epithelial cells and with the transitional epithelium, and the inner longitudinal and outer circular muscle layers of the ureter. No staining could be detected in the lamina propria or in the fat tissue surrounding the ureter.

Effect of administration of growth hormone on plasma and intracellular levels of thyroxine and tri-iodothyronine in thyroidectomized thyroxine-treated rats

1992 ◽  
Vol 133 (1) ◽  
pp. 45-49 ◽  
Author(s):  
P. H. L. M. Geelhoed-Duijvestijn ◽  
F. Roelfsema ◽  
J. P. Schröder-van der Elst ◽  
J. van Doorn ◽  
D. van der Heide
Keyword(s):  
Body Weight ◽  
Type I ◽  
Hormone Metabolism ◽  
Lower Plasma ◽  
Thyroid Hormone Metabolism ◽  
Deiodinase Activity ◽  
Appearance Rate ◽  
Male Wistar Rats ◽  
Wet Weight ◽  
Peripheral Production

ABSTRACT We have studied the effects of the administration of GH on plasma levels and peripheral production of tri-iodothyronine (T3) from thyroxine (T4) in thyroidectomized male Wistar rats given a continuous i.v. infusion of T4 (1 μg/100 g body weight per day) and GH (120 μg per day) for 3 weeks. Tracer doses of 131I-labelled T3 and 125I-labelled T4 were added to the infusion. At isotopic equilibrium (10 days after the addition of 125I-labelled T4) the rats were bled and perfused. The plasma appearance rate for T3 was higher (10·6±1·3 vs 8·4 ± 2·8 pmol/h per 100 g body weight, P = 0·05) and plasma TSH was lower (246±24 vs 470±135 pmol/l, P<0·01) in GH-treated rats. The amount of T3 in liver (12·3 ±2·8 vs 5·5 ± 1·7 pmol/g wet weight, P<0·01), kidney (11·5±1·4 vs 6·5± 1·4 pmol/g wet weight, P <0·01) and pituitary (8·8 ±2·7 vs 4·8±0·5 pmol/g wet weight, P< 0·01) was higher than in controls, mainly as a result of an increased local production of T3 from T4, but plasma-derived T3 was also higher in most organs. We found an increased intracellular T3 concentration in the pituitary which may be responsible for the lower plasma TSH concentration in the GH-treated rats. Since the increase in locally produced T3 is found particularly in liver, kidney and pituitary, typical organs that express 5′-deiodinase activity, we suggest that GH acts on thyroid hormone metabolism by stimulating type-I deiodinase activity. Journal of Endocrinology (1992) 133, 45–49

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