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Biomedical subjects

J R Arthur

Publications and source records attributed to J R Arthur.

At least 55 records · Page 3Linked to original sources
PubMed1994

Hormone-nuclear receptor interactions in health and disease. The iodothyronine deiodinases and 5'-deiodination.

Two types of iodothyronine deiodinase (ID-I and ID-II) catalyse the 5'-deiodination of thyroxine (T4) to produce the biologically active triiodothyronine (T3). Under normal circumstances ID-I in liver and kidney provides the main source of T3 to the circulation, whilst ID-II is largely responsible for local T3 production in the CNS, brown adipose tissue and pituitary. In some circumstances ID-II in brown adipose tissue and ID-I in the thyroid may provide a significant source of plasma T3, and ID-I in the pituitary may be important for local T3 production in this gland. The IDs thus play a pivotal role in controlling the supply of T3 to the nuclear receptors. ID-I is a selenoenzyme and, although ID-II activity is reduced in selenium deficiency, this is a consequence of increased plasma T4 concentration, rather than ID-II activity being directly dependent on selenium. Changes in 5'-deiodination occur in a number of situations such as poor nutrition, illness, iodine and selenium deficiency, and drug therapy. In iodine deficiency these changes appear to have evolved to ensure that the plasma T3 level is maintained and also to provide the brain with a degree of protection from hypothyroxinaemia. Relatively little is known about the importance of selenium deficiency on thyroid function in humans but, in combination with iodine deficiency, selenium deficiency may prove to be a contributing factor in the pathogenesis of myxodematous cretinism. The changes that occur in ID-I and ID-II in illness produce abnormalities in thyroid function tests which, although of no direct clinical significance, may lead to interpretative problems.

Animals↗
PubMed1994

Characterization and postnatal development of 5'-deiodinase activity in goat perirenal fat.

The capacity to generate the active thyroid hormone 3,3',5-triiodothyronine (T3) from thyroxine (T4) has been assessed in the major adipose tissue depot (perirenal) of newborn goats through measurements of iodothyronine 5'-deiodinase activity. High activity of the enzyme was found in the perirenal adipose tissue. Developmental studies demonstrated that there was a rise, then a fall, in iodothyronine 5'-deiodinase activity (per milligram of protein) over the first week of postnatal life, with a further decline between the second and third weeks. At 3 wk of age, the activity per gram of tissue was only 2% of that of the newborn; however, because of age-related increases in the lipid content of the perirenal adipose tissue, the activity per cell (per microgram of DNA) at 3 wk of age was approximately 10% of the activity in the newborn. Kinetic studies and inhibition characteristics with propylthiouracil, gold thioglucose, and T4 indicated that the iodothyronine 5'-deiodinase in goat perirenal adipose tissue is of the type I form; there was no evidence for the type II enzyme. Affinity labeling of the iodothyronine 5'-deiodinase with bromoacetyl-rT3 or bromoacetyl-T4 was consistent with this view. In contrast to goats, only the type II enzyme is evident in rats and mice. It is concluded that the perirenal (brown) adipose tissue is likely to be a significant source of T3 for other tissues in newborn goats and that there are major species variations in the form of iodothyronine 5'-deiodinase present in brown fat, with the goat exclusively exhibiting type I.

Adipose Tissue↗
PubMed1994

First North American record of the marine leech Notostomum laeve (Annelida: Hirudinea).

The Arctic marine leech Notostomum laeve is reported for the first time from North America. A single, small specimen was collected in April 1990 on the external surface of 1 of 30 Greenland halibut Reinhardtius hippoglossoides from Cumberland Sound, Baffin Island, Northwest Territories, Canada. Total length of the specimen including suckers is 41 mm; maximum body width is 1.8 mm. The species is easily identified by the unusual suckers. The caudal sucker is divided into 2 lateral halves that appear to close somewhat like a clam shell; the oral sucker is very thick and muscular with a row of small, hard teeth-like papillae around the outer margin. On the basis of this report from northern Canada, N. laeve probably has a circumpolar distribution in the Arctic Ocean.

Animals↗
PubMed1994

Redescription of Trichodina kamchatika Konovalov, Shevlyakov et Krasin, 1970 (Ciliophora: Peritrichida) from the brook trout (Salvelinus fontinalis) of eastern Canada.

Trichodina kamchatika Konovalov, Shevlyakov et Krasin, 1970 is redescribed based on specimens obtained from the gills and body surface of brook trout (Salvelinus fontinalis) from Nova Scotia and Quebec, Canada and its taxonomic history briefly reviewed. This is the first report of T. kamchatika from North America.

Animals↗
PubMed1993

Presence of the brown fat-specific mitochondrial uncoupling protein and iodothyronine 5'-deiodinase activity in subcutaneous adipose tissue of neonatal lambs.

Subcutaneous adipose tissue of neonatal lambs has been examined for the presence of markers diagnostic of thermogenic brown fat. Uncoupling protein, uncoupling protein mRNA, and iodothyronine 5'-deiodinase activity were each detected in subcutaneous adipose tissue, as well as in the major internal fat depot (perirenal), of newborn lambs. These brown fat markers were not present, however, in adipose tissue of adult sheep. It is concluded that subcutaneous fat in newborn lambs is functionally 'brown', and similar to the internal fat; subcutaneous and internal adipose tissues follow a similar developmental path--from 'brown' to 'white'.

Adipose Tissue↗
PubMed1993

Free radicals and calcium homeostasis: relevance to malignant hyperthermia?

The regulation of intracellular free calcium ions (Ca2+) in skeletal muscle at rest and during contraction depends on mechanisms such as Na(+)-Ca2+ exchangers, Ca(2+)-ATPases, and the voltage-sensitive ryanodine receptor. The susceptibility of these regulatory mechanisms to free-radical-mediated damage may be increased because of their location within the lipid membranes of sarcolemma, sarcoplasmic reticulum, and mitochondrion with resultant uncontrolled increases in myoplasmic Ca2+ concentration and cell death. The potentially fatal pharmacogenetic disorder, malignant hyperthermia (MH), is characterised by muscle rigidity, arrhythmias, lactic acidosis, and a rapid rise in body temperature. The sequence of events responsible for the MH syndrome remains uncertain, but it has been variously ascribed to faults in many of the Ca2+ regulatory mechanisms. In swine the condition is associated with a specific mutation in the ryanodine receptor, whereas in humans the syndrome is genetically heterogenous. Free-radical-mediated peroxidation of membrane lipids and proteins also results in the rapid efflux of Ca2+ from organelles, and the detection of products of free radical reactions in tissue from MH-susceptible individuals using electron spin resonance spectroscopy provides evidence for the involvement of free radicals in the MH syndrome.

Animals↗
PubMed1993

Selenium deficiency, thyroid hormone metabolism, and thyroid hormone deiodinases.

Much research into the functions of selenium in the cell has concentrated on its role in selenium-containing glutathione peroxidases. However, selenium was recently shown to be an essential component of type I iodothyronine 5'-deiodinase in rats, which converts thyroxin to the more biologically active hormone 3,5,3'-triiodothyronine. Thus, selenium-deficient rats have low tissue deiodinase activities and abnormal thyroid hormone metabolism. The discovery of this function for selenium in thyroid hormone metabolism has important implications for the interpretation of the effects of selenium deficiency, especially in individuals with an adequate vitamin E status.

Animals↗
PubMed1993

Effects of combined iodine and selenium deficiency on thyroid hormone metabolism in rats.

This paper compares the effects of combined iodine and selenium deficiency, of single deficiencies of these trace elements, and of no deficiency on thyroid hormone metabolism in rats. In rats deficient in both trace elements, thyroidal triiodothyronine (T3), thyroidal thyroxin (T4), thyroidal total iodine, hepatic T4, and plasma T4 were significantly lower, and plasma thyroid-stimulating hormone (TSH) and thyroid weight were significantly higher than in rats deficient in iodine alone. Plasma and hepatic T3 concentrations were similar in the dietary groups. Hepatic type I iodothyronine deiodinase (ID-I) activity was inhibited by selenium deficiency irrespective of the iodine status. Type II deiodinase (ID-II) activity in the brain was significantly higher and in pituitary, significantly lower in combined deficiency than in iodine deficiency alone. These data show that selenium can play an important role in determining the severity of the hypothyroidism associated with iodine deficiency.

Animals↗
PubMed1993

The role of thyroidal type-I iodothyronine deiodinase in tri-iodothyronine production by human and sheep thyrocytes in primary culture.

We have studied the origin of tri-iodothyronine (T3) secreted by human and sheep thyrocytes in primary culture and also the expression of type-I thyroidal iodothyronine deiodinase (ID-I) in the thyroid and liver of man and various other animals. Inhibitors of ID-I reduced T3 secretion from human but not sheep thyrocytes. In contrast, inhibitors of de-novo thyroid hormone synthesis reduced both thyroxine (T4) and T3 production in sheep thyrocytes, but had no effect on the T3 secreted by human thyrocytes. Human thyrocytes did not produce T4 under the culture conditions used, although some endogenous T4 was present in the cells following their isolation. Although thyrotrophin (TSH) stimulated T3 production in both human and sheep thyrocytes, iodine in the form of potassium iodide was only essential for T3 and T4 production by the sheep cells. Although 125I from Na125I was incorporated into T3 and T4 in TSH-stimulated sheep thyrocytes, no 125I incorporation into T3 or T4 was detected in TSH-stimulated human thyrocytes. Using activity measurements and affinity labelling, ID-I was present in the livers of all species studied, but ID-I could not be detected in thyroid tissue from cattle, pigs, sheep, goats, rabbits, deer or llamas. In contrast, thyroid tissue from man, mice, guinea-pigs and rats had significant ID-I activity and expressed an affinity-labelled protein with a molecular mass of approximately 28.1 kDa on SDS-PAGE. These data show that under the culture conditions used, sheep thyrocytes produced T3 by de-novo synthesis, whilst human thyrocytes produced T3 by deiodination of endogenous T4. We conclude that thyroidal ID-I shows marked species difference in its expression and that, in those species which express the enzyme (man, mice, guinea-pigs and rats, in this study), it appears that it may make an important contribution to thyroidal T3 production.

Animals↗
PubMed1992

Lipid peroxidation, antioxidant concentrations, and fatty acid contents of muscle tissue from malignant hyperthermia-susceptible swine.

Homogenates of semitendinosus muscle from malignant hyperthermia (MH)-susceptible pigs produced threefold more pentane than those from MH-resistant pigs, indicating enhanced free radical-mediated peroxidation of n-6 fatty acids. This did not reflect a deficiency in tissue antioxidants or antioxidant-enzymes but glutathione concentrations and glutathione peroxidase activities were increased in the tissue from MH-susceptible swine, consistent with an adaptive response to a sustained oxidant stress. A lower proportion of linoleic acid (18:2 n-6) in phospholipids and neutral lipids in muscle from MHS pigs indicated increased peroxidation or metabolism (desaturation and elongation). The increased oleic acid (18:1 n-9) in the MHS muscle indicated that desaturase activity was elevated in all lipid classes. The results are consistent with the hypothesis that enhanced free radical activity and lipid peroxidation contributes to the abnormalities in Ca2+ homeostasis and polyunsaturated fatty acid metabolism in MH.

Animals↗
PubMed1992

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

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.

Animals↗
PubMed1992

The role of selenium in thyroid hormone metabolism and effects of selenium deficiency on thyroid hormone and iodine metabolism.

Selenium deficiency impairs thyroid hormone metabolism by inhibiting the synthesis and activity of the iodothyronine deiodinases, which convert thyroxine (T4) to the more metabolically active 3,3'-5 triiodothyronine (T3). Hepatic type I iodothyronine deiodinase, identified in partially purified cell fractions using affinity labeling with [125I]N-bromoacetyl reverse triiodothyronine, is also labeled with 75Se by in vivo treatment of rats with 75Se-Na2SeO3. Thus, the type I iodothyronine 5'-deiodinase is a selenoenzyme. In rats, concurrent selenium and iodine deficiency produces greater increases in thyroid weight and plasma thyrotrophin than iodine deficiency alone. These results indicate that a concurrent selenium deficiency could be a major determinant of the severity of iodine deficiency.

Animals↗
PubMed1992

Selenium deficiency and type II 5'-deiodinase regulation in the euthyroid and hypothyroid rat: evidence of a direct effect of thyroxine.

Selenium deficiency in rats is characterized by elevated serum T4 and decreased serum T3 concentrations, and low liver type I (5'D-I) and brain type II (5'D-II) iodothyronine 5'-deiodinase activities. These findings are partially explained by the demonstration that type I 5'D is a selenoprotein; however, 5'D-II does not contain selenium. Since 5'D-II varies inversely with serum T4 concentrations, and serum T4 is elevated in selenium deficiency, the decreased cerebrocortical 5'D-II activity may be secondary to the increased serum T4 levels. To determine the mechanism(s) by which selenium influences 5'D-II activity, we examined the effects of altered selenium intake on brain 5'D-II levels and enzyme turnover in euthyroid and thyroidectomized rats. Rats were fed a selenium-supplemented or selenium-deficient diet for 5 weeks from weaning; half of the animals were also thyroidectomized 3 weeks before death. Selenium deficiency was confirmed by decreased liver and brain glutathione peroxidase activities. In euthyroid rats, selenium deficiency caused a 38% increase in serum T4, and 91% and 39% decreases in 5'D-I and 5'D-II, respectively, compared to those in selenium-supplemented rats. In the thyroidectomized hypothyroid rats, selenium deficiency caused a 60% decrease in 5'D-I, but had no effect on 5'D-II activity, fractional turnover of the enzyme, or the calculated enzyme synthesis rate. The lack of effect of selenium deficiency on 5'D-II levels in hypothyroid rats is consistent with the finding that 5'D-II is not a seleno-enzyme. Thus, the decrease in brain and pituitary 5'D-II activity in selenium-deficient euthyroid rats is due to the T4-dependent increase in the turnover of the enzyme polypeptide.

Animals↗
PubMed1992

Effects of selenium deficiency on thyroid hormone economy in rats.

In selenium-deficient rats, peripheral T4 to T3 conversion is markedly decreased due to the loss of the selenoprotein, type I iodothyronine 5'-deiodinase (5'D-I). Despite the marked increase in circulating T4 that results from this loss of 5'D-I, serum T3 concentrations in selenium-deficient rats remain in the normal range. To determine the physiological mechanism(s) that maintains circulating T3 when peripheral T4 to T3 conversion is impaired, we examined the interrelationships between selenium intake and the metabolism of T3 and T4 in the rat. In euthyroid rats, selenium deficiency caused the expected loss of 5'D-I, with a 52% increase in serum T4, which paralleled an increase in the T4 biological half-life. Consistent with the prolonged t1/2 of T4, short term thyroidectomy (48 h) in selenium-deficient rats failed to decrease serum T4 concentrations to the levels observed in short term thyroidectomized, selenium-supplemented rats. Short term thyroidectomy also caused an expected 33% decrease in liver 5'D-I and a 44% increase in brain type II iodothyronine 5'-deiodinase (5'D-II) activities in selenium-supplemented rats. However, in selenium-deficient rats, short term thyroidectomy did not affect 5'D-I or 5'D-II activities. In contrast to the selenium-dependent changes in circulating T4 levels, little or no change in circulating T3 concentrations occurred. There was a 20% increase in the T3 half-life in selenium-deficient rats. The serum T3 sulfate concentration was increased, and T3 deiodination was reciprocally decreased in the selenium-deficient rats. These data suggest that increased T3 sulfate generation in selenium-deficient rats may lead to greater T3 availability through enterohepatic recycling of the iodothyronine and may explain why there are only minor changes in serum T3 concentrations in selenium-deficient rats.

Animals↗
PubMed1991

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

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.

Affinity Labels↗