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U.S. Department of Agriculture, Agricultural Research Service, Western Human Nutrition Research Center and Department of Nutrition, University of California at Davis, Davis, CA
3To whom correspondence should be addressed. E-mail: chawkes{at}whnrc.usda.gov.
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ABSTRACT |
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 TOP ABSTRACT SUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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KEY WORDS: • selenium • thyroid • thyrotropin • body weight • energy metabolism
Selenocysteine is an essential component of several enzymes. There are four selenium-dependent glutathione peroxidases known in humans (1–4). They are encoded by separate genes and protect against oxidative damage by reducing hydrogen peroxide and other hydroperoxides at the expense of glutathione. In humans, there are three forms of thioredoxin reductase, an antioxidant enzyme important in regulation of the cell cycle that was recently shown to be a selenocysteine-containing enzyme (5), as was selenophosphate synthetase, which forms the activated selenium precursor for synthesis of selenocysteine (6). Many other selenocysteine-containing proteins have been reported, but their functions are not known (7–10).
A major advance in our understanding of selenium’s role in metabolism began with the discovery that type I iodothyronine deiodinase, the enzyme responsible in humans for most of the peripheral conversion of thyroxine (T4)3 to the active form 3,3',5-triiodothyronine (T3), is a selenoenzyme (11,12). More recently it was discovered that the type II deiodinase (responsible for T4 conversion to T3 in the brain) and the type III deiodinase (the inner ring deiodinase responsible for deactivating T4 and T3) are also selenocysteine enzymes (13,14). Extracellular glutathione peroxidase is expressed at a high level in thyroid follicular cells and is excreted into the follicular lumen, where indirect control of thyroglobulin iodination is thought to occur by regulation of hydrogen peroxide concentrations (15). Thus, selenoenzymes may modulate or control many aspects of thyroid hormone metabolism: iodination of thyroglobulin in the thyroid gland; peripheral synthesis of T3 from T4; degradation of T4 to 3,3',5'-triiodothyronine ("reverse T3", rT3); inactivation of T3 to 3,3'-diiodothyronine; and regulation of thyroidal activity by the pituitary-hypothalamic axis (16). Thyroid hormone metabolism is sensitive to the total energy content of the diet and the amount of carbohydrate (17), and it may also be affected by other dietary components, including iodine (18), iron (19), zinc (20), copper (21), manganese (22) and methionine (23), as well as certain goitrogenic substances such as cyanide compounds in cassava (24).
In adults, the major effects of thyroid hormone are on energy metabolism. In the hyperthyroid state, thermogenesis, and thus the basal metabolic rate, is increased and body weight tends to decrease. In the hypothyroid state, thermogenesis and basal metabolic rate are decreased and body weight tends to increase. There are effective treatments available for both hyperthyroidism and hypothyroidism (25), but the significance and treatment of subclinical hyperthyroidism and hypothyroidism remain controversial (26,27). Genes related to energy metabolism whose expression is known to be regulated by T3 include malic enzyme in the liver (28), 
-myosin heavy chain in heart (29), uncoupling protein-3 in skeletal muscle (30), type I deiodinase in liver (31) and thyroid-stimulating hormone (thyrotropin, TSH) in the pituitary (32).
Studies of selenium and thyroid hormone metabolism have been conducted in rats. Unfortunately, studies in rats cannot be extrapolated to humans because circulating T3 is produced mainly by deiodination of T4 in liver in humans (17), but comes primarily by release from the thyroid in rats (16). The human and rat type I deiodinase enzymes are also different in several respects, including amino acid sequence, molecular weight (33) and sensitivity to inhibition with propylthiouracil (34). Most studies of selenium and thyroid hormone have used sodium selenite as the source of dietary selenium. However, selenite is an insignificant source of selenium in human diets (except for some selenium supplements) and possesses potent pharmacologic activities unrelated to the nutritional requirement for selenium, including prooxidant (35), insulin-mimetic (36), glutathione-depleting (37) and RNA synthesis–inhibiting (38) activities. On the other hand, selenium in food occurs primarily as derivatives of the amino acids selenocysteine and selenomethionine (39–41). Selenium is catabolized to Se-2 and used for de novo synthesis of selenocysteine-containing proteins, which express selenium’s nutritional effects as enzyme activities (41). Selenium from selenomethionine in excess of nutritional requirements is incorporated nonspecifically into proteins in place of methionine, apparently without regulation, whereas excess selenium in other forms tends to be excreted efficiently in the urine. We hypothesized that the effects of selenium in food in humans would be different from the reported effects of selenite in rats.
We fed 11 men a controlled diet of conventional foods with naturally high or low selenium contents for 120 d while confined to a metabolic research unit to identify the metabolic effects in humans of dietary selenium as it occurs naturally in foods. In this report, we present results describing novel effects of these diets on thyroid hormone and energy metabolism, body weight and body composition.
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SUBJECTS AND METHODS |
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TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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Healthy male volunteers (n = 12) were recruited and confined in a metabolic research unit for 120 d under 24-h supervision by staff members and fed a diet composed of conventional foods naturally high or low in selenium as previously described (42). Because this study was not originally intended to study energy metabolism, if body weight subsequently changed by >1% from baseline, energy intake was adjusted in increments of 0.4 MJ/d. When energy intake was changed, all components of the diet were adjusted proportionally such that the relative composition of the diet did not change. This led to the following energy intake changes in the low selenium group during the intervention period: 3 subjects’ energy intakes were held constant throughout; one subject’s energy intake was increased by 0.4 MJ/d on d 63 and then increased by a further 0.4 MJ/d on d 92; another subject’s energy intake was decreased by 0.4 MJ/d on d 63 and then decreased by a further 0.4 MJ/d on d 92; and, a third subject’s energy intake was increased by 0.4 MJ/d on d 39, for a net increase of 0.07 MJ/d in the low selenium group’s mean energy intake. In the high selenium group during the intervention period, 3 subject’s energy intakes were held constant throughout, one subject’s energy intake was decreased by 0.4 MJ/d on d 70, and another subject’s energy intake was increased by 0.8 MJ/d on d 96, for a net increase of 0.08 MJ/d in the high selenium group’s mean energy intake. These deliberate changes in energy intake were similar in magnitude to the random weighing errors and menu variations in energy content, which caused daily energy intake to vary with a SD of 0.075 MJ/d.
Because the amounts and chemical form of selenium given to the subjects as stable isotopes on d 110 were different from the selenium in the foods, a blood sample was obtained from all subjects the morning of d 110 before the stable isotope was administered, and only the biochemical data up to d 110 are presented here. The weight changes were already significant before the stable isotope administration and continued the same trend afterwards; thus, these data are presented for the entire 120-d study period.
Laboratory measurements.
Blood samples were collected at 0700 h, after an overnight fast of 12 h. Blood samples for clinical chemistries were clotted, and the serum was separated by centrifugation at 1200 x g for 15 min and refrigerated until analyzed each night at a reference laboratory ("Chemzyme Plus," Smith-Kline Beecham, Santa Cruz, CA). Aliquots of serum were stored at -70°C. Total T4, total T3 and total rT3 were measured by RIA in 12 mm x 75 mm tubes (Coat-A-Count, Diagnostic Products, Los Angeles, CA), and TSH was measured by immunoradiometric assay (Coat-A-Count IRMA, Diagnostic Products).
Body composition measurements.
Subjects were weighed daily between 0700 and 0715 h, after urinating to empty their bladders and before eating breakfast. Subjects wore standard hospital gowns for all weight measurements. Body composition was determined in wk 3, 10 and 17 by total body electrical conductivity using the HA-2 body composition analyzer (EM-SCAN, Springfield, IL). A prediction equation specific for healthy men was used to estimate fat-free mass from body conductivity (43). Body fat mass was calculated by subtracting fat-free mass from body weight.
Energy expenditure and utilization.
Resting metabolic rate was measured in wk 3, 10 and 17. All measurements were made in the morning before breakfast after a 12-h overnight fast. Subjects rested quietly in a semireclined position for 20 min, and then measurements of oxygen consumption and carbon dioxide production were taken during the next 15 min using an automated respiratory gas exchange system (Model 2900, SensorMedics, Anaheim, CA). The system was calibrated with standard gas mixtures. Resting metabolic rate was calculated using the Weir equation, including a correction for urinary nitrogen (44). Pulse, respiration and temperature were measured once a week in the morning before rising. Heart rates were measured for 24 h periods during wk 3, 10 and 17 using Holter electrocardiograph recorders (Del Mar Avionics, Irvine, CA).
Statistical analysis.
Effects of dietary selenium were determined using repeated-measures ANOVA, controlling for each subject’s baseline value, or by a t test of the within-subject changes when only a baseline and final measurement were made. The ANOVA calculations were performed with BMDP 7.0 program 2V, Analysis of Variance and Covariance with Repeated Measures (Los Angeles, CA). The ANOVA included a complete model: Selenium, Time, Covariate (baseline value), and Selenium x Time. A two-tailed probability 
0.05 was considered significant. Effects of food selenium were detected as significant Selenium main effects or Selenium x Time interactions, and the Student-Newman-Keuls multiple comparison test was used to identify significant differences between the groups at individual time points. The estimates of data variability are SD, unless otherwise noted.
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RESULTS |
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TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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Controlling the geographic source of the rice and beef in otherwise identical diets resulted in constant daily selenium intakes of 47, 14 and 297 µg/d (595, 177 and 3760 nmol/d) from the stabilization, low selenium and high selenium diets, respectively, at the mean energy intake of 11.7 MJ/d (42). These intakes are similar to the amount required to maintain glutathione peroxidase activity in plasma (45), less than the minimum human requirement to prevent Keshan disease (46) and similar to typical human intakes in South Dakota (47), respectively. The low selenium diet and the high selenium diet significantly altered tissue selenium concentrations and glutathione peroxidase activities, reflecting physiologic changes in selenium nutritional status (42). The low selenium diet decreased selenium concentration by 34% in plasma, 26% in RBC and 19% in skeletal muscle, whereas the high selenium diet increased selenium concentrations 85, 66 and 38%, respectively, in these tissues (42).
Thyroid hormone status.
The high and low selenium diets led to changes in serum T3 that were significantly different between groups (P = 0.013; Table 1) (Fig. 1). The maximum serum T3 response was observed at d 45, the first measurement after the diet change, with a 14% increase in the low selenium group and a 23% decrease in the high selenium group. The changes in serum T3 remained significantly different throughout the study, ending 8% higher and 11% lower in the low selenium and high selenium groups, respectively. Serum TSH increased significantly only in the high selenium group (P = 0.031, t test of within-subject changes) (Fig. 2). The increase of TSH on d 45 was significant in the high selenium group. T4 and rT3 concentrations in serum did not differ between groups, although the concentrations of these iodothyronines declined by 14 and 30%, respectively, in both groups during the study (Table 1). All thyroid variables measured were within the normal range in all subjects at all time points. There was no difference between groups in total cholesterol, HDL cholesterol, LDL cholesterol, triacylglycerol, glucose, urea nitrogen or total protein in serum (data not shown). The clinical blood chemistry values were within normal ranges for all subjects at all time points and did not show any other changes attributable to the diet (42).
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(Table 1). Body weights were stabilized during the 21-d baseline period and remained stable through d 57 (Fig. 3). However, by d 64, body weights in the high selenium group began to increase relative to the low selenium group. This difference became significant by d 92 and remained so for the rest of the study (P = 0.0001, Se x Time interaction). Body fat mass decreased by a mean of 1.7 ± 1.2 kg in the low selenium group (paired t test, P = 0.021). Fat-free mass increased by a mean of 1.3 ± 0.8 kg in both groups. Serum triacylglycerol concentrations (Fig. 4) increased when T3 concentrations increased in the low selenium group and decreased when T3 concentrations decreased in the high selenium group (P = 0.025, Se main effect), indicating a difference in fat metabolism between the high and low selenium groups. The groups did not differ in energy intake, resting oxygen consumption, respiratory exchange ratio, 24-h heart rate, mean arterial blood pressure or urinary nitrogen excretion (data not shown).
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DISCUSSION |
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TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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Most selenium depletion studies in rats have noted increased T4 and rT3, and decreased T3 (34,48). In the present study, only T3 responded to selenium and in the opposite direction, increasing when selenium was restricted and decreasing when selenium was increased. This difference may be due to the fact that serum T3 in humans comes mainly by deiodination of T4 in liver (17), whereas serum T3 in rats is released mainly preformed from the thyroid (16), which may be related to differences in the regulation of type I activity by selenium in thyroid and liver (49) as well as differences in the properties of the type I enzymes in humans and rats (33,34). There is, however, one report that high dietary selenium increased thyrotropin in rat serum (50), consistent with our observations in humans. It is also relevant that most rat studies induced a state of profound selenium deficiency, with glutathione peroxidase activities suppressed by as much as 90%, whereas we induced only a mild depletion, with only a 12% decrease in plasma glutathione peroxidase activity in the low selenium group.
The effects of selenium depletion in rats have been rationalized as reflecting decreased expression of the peripheral type I selenodeiodinase enzyme responsible for converting T4 to T3 and rT3 to 3,3'-diiodothyronine (11). However, there is at least one human study that suggests that type I selenodeiodinase may be regulated by selenium oppositely from rats. Mothers in seleniferous areas of Venezuela with higher blood selenium tended to have lower T3, which was attributed to a depression of type I selenodeiodinase activity by high dietary selenium intakes (51), consistent with the decrease in T3 in our high selenium group. There are also a few reports of effects of selenium on thyroid hormones different from what we observed, but only in persons with health problems, i.e., severely selenium-deficient phenylketonuric children (52), cystic fibrosis patients (mean age 13.8 y) (53) and institutionalized elderly (54).
Circulating concentrations of T4 and rT3 decreased by 
14 and 30%, respectively, in both groups during the study. Decreased thyroid hormone concentrations are frequently observed in confined human metabolic studies and may be related to the carbohydrate content of the experimental diets (55) or to the decreased dietary iodine intake compared with the subjects’ estimated prestudy diets (18). However, the T3, T4, rT3, TSH (Table 1) and other clinical chemistry values (42) were within normal ranges for all subjects at all times. Because we used real foods from different parts of the world, we cannot completely exclude the possibility that some constituent of the diet other than selenium influenced the effects we observed. However, each of the three experimental diets was analyzed for all of the dietary components known to affect thyroid hormone or energy metabolism and no differences exceeding the analytical error of the methods were found (42).
The weight changes observed in this study were consistent with the known metabolic effects of thyroid hormone and with the observed changes in serum T3. Treatment of hypothyroidism (56,57) and T3 administration (58,59) cause weight loss in humans, and hypothyroidism (57) and treatment of hyperthyroidism (56) cause weight gain. Although there were some minor changes made to the subjects’ energy intakes that might have affected T3 (17), there is little basis to suspect this was responsible for the observed weight changes. The increase in mean energy intake was similar in both groups (0.07–0.08 MJ/d) and is too small to account for the different weight changes between groups. In addition, the low selenium group lost weight despite a slight increase in energy intake, and the weight gains in the high selenium group were already significant before any subject’s energy intake was increased. Furthermore, the mean cumulative energy intake increase in the high selenium group of 1.92 MJ per subject was considerably smaller than the energy equivalent of the mean weight gain of 0.7 kg, even if it were all lean tissue.
We observed no changes in resting metabolic rate or body temperature that would indicate a change in the basal rate of energy expenditure. However, the daily energy balance would have had to change by only 0.25 MJ/d to account for the mean weight gain of 0.7 kg (even if it were all fat tissue), a shift that would not have been detectable with the energy expenditure measurements used. There have been other reports of T3-induced weight losses in humans without significant changes in basal metabolic rate (58) or oxygen consumption (59). The study protocol prescribed two 3.2-km walks every day and prohibited any other form of exercise. Nevertheless, the subjects may have had significantly different energy expenditures due to voluntary activities that were not reflected in the resting oxygen consumption rates or the 24-h heart rates. Any such effect would have been randomly distributed between the two groups, unless it was due to the diets. There is at least one possible mechanism whereby selenium could change voluntary activity levels and affect energy balance independently of thyroid hormone, i.e., a beneficial effect of dietary selenium on mood, including anxiety, depression and tiredness (60,61). No significant changes in mood scores were observed in our subjects (62). However, we cannot rule out the possibility that high selenium intakes decreased anxiety, leading to less voluntary activity ("fidgeting"), a positive energy balance and weight gain, or vice versa.
Although the increased serum triacylglycerol and decreased body fat in the low selenium group suggest that lipolysis was increased by serum T3 as has been reported by others (57,63,64), the respiratory gas exchange ratio did not indicate any significant changes in carbohydrate or fat utilization rates after the baseline period. This was not unexpected, however, because the changes in daily carbohydrate and fat utilization rates required to explain the observed changes in body composition would have been too small to detect by the indirect calorimetry methods used. Increased serum triacylglycerol driven by thyroid hormone has also been reported in selenium-deficient rabbits fed a high fat diet (49). Our observation that weight loss in the low selenium group was not accompanied by loss of lean tissue is consistent with previous reports of T3 -induced weight loss without changes in nitrogen balance (59) or protein turnover (58).
These small changes in body weight seem unimportant for healthy adult men. It is tempting to speculate that the body’s homeostatic mechanisms would eventually adapt to a high selenium intake and restore energy balance and weight maintenance. On the other hand, a simple extrapolation suggests that if the effect of high dietary selenium were to persist, it could cause a weight gain of up to 12 kg in 5 y. This would be a noteworthy rate of weight increase compared with the typical weight gain in men of 1.4–4 kg in 5 y (65–67). This potential adverse effect of dietary selenium deserves further attention in light of the report of dramatic cancer-preventive benefits from supplementation with 200 µg /d (2.5 µmol/d) of selenium (68), corresponding to a total selenium intake similar to that of our high selenium group. On the other hand, selenium-induced weight gain might be an unanticipated benefit of selenium treatment in current and proposed clinical trials for AIDS (69) and cancer (68).
The results suggest that changes in the activities of selenoenzymes involved in thyroid hormone metabolism led to shifts in circulating T3 concentrations and perturbations of the pituitary-thyroid axis. The resulting subclinical hypothyroid and hyperthyroid responses caused changes in the expenditure of metabolic energy leading to gradual changes in body weight and composition, which, over time, might be physiologically important. Much more work will be required to determine the significance of these clinical observations to the general population and to adequately assess the potential risks and benefits of high intakes of selenium from food.
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ACKNOWLEDGMENTS |
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FOOTNOTES |
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2 U.S. Department of Agriculture Agricultural Research Service Project 5306–51530-010–00D supported this research. Mention of trade name, proprietary product, or specific equipment does not constitute a guarantee or warranty by the U.S. Department of Agriculture, nor does it imply approval to the exclusion of other products that may be suitable. The opinions expressed herein represent those of the authors and do not necessarily represent those of the U.S. Department of Agriculture.
4 Abbreviations used: rT3, 3,3',5'-triiodothyronine ("reverse T3"); T3, 3,3',5-triiodothyronine; T4, thyroxine; TSH, thyroid-stimulating hormone, thyrotropin.
Manuscript received 23 May 2003. Initial review completed 7 July 2003. Revision accepted 21 August 2003.
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LITERATURE CITED |
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TOPABSTRACTSUBJECTS AND METHODSRESULTSDISCUSSIONLITERATURE CITED |
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1. Mills, G. C. (1959) The purification and properties of glutathione peroxidase of erythrocytes. J. Biol. Chem. 234:502-506.
2. Takahashi, K., Avissar, N., Whitin, J. & Cohen, H. (1987) Purification and characterization of human plasma glutathione peroxidase a selenoglycoprotein distinct from the known cellular enzyme. Arch. Biochem. Biophys. 256:677-686.[Medline]
3. Zhang, L., Maiorino, M., Roveri, A. & Ursini, F. (1989) Phospholipid hydroperoxide glutathione peroxidase specific activity in tissues of rats of different age and comparison with other glutathione peroxidases. Biochim. Biophys. Acta 1006:140-143.[Medline]
4. Chu, F. F., DeSilva, H.A.R., Esworthy, R. S., Boteva, K. K., Walters, C. E., Roses, A., Rao, P. N. & Pettenati, M. J. (1996) Polymorphism and chromosomal localization of the GI-form of human glutathione peroxidase (GPX2) on 14q24.1 by in situ hybridization. Genomics 32:272-276.[Medline]
5. Gladyshev, V. N., Jeang, K. T. & Stadtman, T. C. (1996) Selenocysteine, identified as the penultimate C-terminal residue in human T-cell thioredoxin reductase, corresponds to TGA in the human placental gene. Proc. Natl. Acad. Sci. U.S.A. 93:6146-6151.
6. Low, S. C., Harney, J. W. & Berry, M. J. (1995) Cloning and functional characterization of human selenophosphate synthetase, an essential component of selenoprotein synthesis. J. Biol. Chem. 270:21659-21664.
7. Behne, D., Weissnowak, C., Kalcklosch, M., Westphal, C., Gessner, H. & Kyriakopoulos, A. (1995) Studies on the distribution and characteristics of new mammalian selenium-containing proteins. Analyst 120:823-825.[Medline]
8. Hawkes, W. C., Wilhelmsen, E. C. & Tappel, A. L. (1985) Abundance and tissue distribution of selenocysteine-containing proteins in the rat. J. Inorg. Biochem. 23:77-92.[Medline]
9. Hawkes, W. C., Wilhelmsen, E. C. & Tappel, A. L. (1985) Subcellular distribution of selenium-containing proteins in the rat. J. Inorg. Biochem. 25:1-17.
10. Wilhelmsen, E. C., Hawkes, W. C., Motsenbocker, M. A. & Tappel, A. L. (1981) Selenocysteine-containing proteins other than glutathione peroxidase from rat tissue. Spallholz, J. E. Martin, J. L. Ganther, H. E. eds. Selenium in Biology and Medicine 1981 Avi Publishing Westport, CT. .
11. Beckett, G. J., Hutchinson, A. R., Nicol, F. & Arthur, J. R. (1988) A role for selenium in the hepatic 5' deiodination of thyroxine. J. Endocrinol. 117:287.
12. Arthur, J. R. & Beckett, G. J. (1988) Selenium deficiency and thyroid hormone metabolism. Wendel, A. eds. Selenium in Biology and Medicine 1988 Springer-Verlag New York, NY. .
13. Ramauge, M., Pallud, S., Esfandiari, A., Gavaret, J. M., Lennon, A. M., Pierre, M. & Courtin, F. (1996) Evidence that type III iodothyronine deiodinase in rat astrocyte is a selenoprotein. Endocrinology 137:3021-3025.[Abstract]
14. Davey, J. C., Becker, K. B., Schneider, M. J., Stgermain, D. L. & Galton, V. A. (1995) Cloning of a cDNA for the type II iodothyronine deiodinase. J. Biol. Chem. 270:26786-26789.
15. Howie, A. F., Walker, S. W., Akesson, B., Arthur, J. R. & Beckett, G. J. (1995) Thyroidal extracellular glutathione peroxidase: a potential regulator of thyroid-hormone synthesis. Biochem. J. 308:713-717.
16. Braverman, L. E. (1994) Deiodination of thyroid hormones—a 30 year perspective (Berthold Memorial Award Lecture 1994). Exp. Clin. Endocrinol. 102:355-363.[Medline]
17. Danforth, E., Jr & Burger, A. G. (1989) The impact of nutrition on thyroid hormone physiology and action. Annu. Rev. Nutr. 9:201-207.[Medline]
18. Clugston, G. A. & Hetzel, B. S. (1994) Iodine. Shils, M. E. Olson, J. A. Shike, M. eds. Modern Nutrition in Health and Disease 8th ed. 1994 Lea & Febiger Philadelphia, PA. .
19. Brigham, D. & Beard, J. (1996) Iron and thermoregulation: a review. Crit. Rev. Food. Sci. Nutr. 36:747-763.[Medline]
20. Kralik, A., Eder, K. & Kirchgessner, M. (1996) Influence of zinc and selenium deficiency on parameters relating to thyroid hormone metabolism. Horm. Metab. Res. 28:223-226.[Medline]
21. Kralik, A., Kirchgessner, M. & Eder, K. (1996) Concentrations of thyroid hormones in serum and activity of hepatic 5' monodeiodinase in copper-deficient rats. Z. Ernaehrswiss. 35:288-291.[Medline]
22. Eder, K., Kralik, A. & Kirchgessner, M. (1996) The effect of manganese supply on thyroid hormone metabolism in the offspring of manganese-depleted dams. Biol. Trace Elem. Res. 55:137-145.[Medline]
23. Zhu, Z., Kimura, M. & Itokawa, Y. (1995) Iodothyronine deiodinase activity in methionine-deficient rats fed selenium-deficient or selenium-sufficient diets. Biol. Trace Elem. Res. 48:197-213.[Medline]
24. Abuye, C., Kelbessa, U. & Wolde-Gebriel, S. (1998) Health effects of cassava consumption in south Ethiopia. East Afr. Med. J. 75:166-170.[Medline]
25. Vanderpump, M. P., Ahlquist, J. A., Franklyn, J. A. & Clayton, R. N. (1996) Consensus statement for good practice and audit measures in the management of hypothyroidism and hyperthyroidism. Br. Med. J. 313:539-544.
26. Surks, M. I. & Ocampo, E. (1996) Subclinical thyroid disease. Am. J. Med. 100:217-223.[Medline]
27. Woeber, K. A., Surks, M. I. & Ocampo, E. (1997) Subclinical thyroid dysfunction. Arch. Intern. Med. 157:1065-1068.[Abstract]
28. Petty, K. J., Desvergne, B., Mitsuhashi, T. & Nikodem, V. M. (1990) Identification of a thyroid hormone response element in the malic enzyme gene. J. Biol. Chem. 265:7395-7400.
29. Izumo, S. & Mahdavi, V. (1988) Thyroid hormone receptor alpha isoforms generated by alternative splicing differentially activate myosin HC gene transcription. Nature (Lond.) 334:539-542.[Medline]
30. Gong, D. W., He, Y., Karas, M. & Reitman, M. (1997) Uncoupling protein-3 is a mediator of thermogenesis regulated by thyroid hormone, beta3-adrenergic agonists, and leptin. J. Biol. Chem. 272:24129-24132.
31. Jakobs, T. C., Schmutzler, C., Meissner, J. & Kohrle, J. (1997) The promoter of the human type I 5'-deiodinase gene–mapping of the transcription start site and identification of a DR+4 thyroid-hormone- responsive element. Eur. J. Biochem. 247:288-297.[Medline]
32. Shupnik, M. A., Ridgway, E. C. & Chin, W. W. (1989) Molecular biology of thyrotropin. Endocr. Rev. 10:459-475.[Medline]
33. Santini, F., Chopra, I. J., Hurd, R. E. & Teco, G.N.C. (1992) A study of the characteristics of hepatic iodothyronine 5'-monodeiodinase in various vertebrate species. Endocrinology 131:830-834.[Abstract]
34. Berry, M. J. & Larsen, P. R. (1994) The Role of Selenium in Thyroid Hormone Action 1994 Endocrine Society Bethesda, MD.
35. Shen, H. M., Yang, C. F. & Ong, C. N. (1999) Sodium selenite-induced oxidative stress and apoptosis in human hepatoma HepG(2) cells. Int. J. Cancer 81:820-828.[Medline]
36. Roden, M., Prskavec, M., Furnsinn, C., Elmadfa, I., Konig, J., Schneider, B., Wagner, O. & Waldhausl, W. (1995) Metabolic effect of sodium selenite: insulin-like inhibition of glucagon-stimulated glycogenolysis in the isolated perfused rat liver. Hepatology 22:169-174.[Medline]
37. Caffrey, P. B., Abdullaev, F. & Frenkel, G. D. (1991) Differential cytotoxicity of selenite for tumor cells can be achieved by differential depletion of cellular glutathione. FASEB. J. 5:A580 (abs.).
38. Frenkel, G. D. & Falvey, D. (1989) Involvement of cellular sulfhydryl compounds in the inhibition of RNA synthesis by selenite. Biochem. Pharmacol. 38:2849-2852.[Medline]
39. Wolf, W. R., Zainal, H. & Yager, B. (2001) Selenomethionine content of candidate reference materials. Fresenius J. Anal. Chem. 370:286-290.[Medline]
40. Wolf, W. R. & Zainal, H. (2002) Methylseleno-amino acid content of food materials by stable isotope dilution mass spectrometry. Food Nutr. Bull. 23:120-123.[Medline]
41. Combs, G. F., Jr (2001) Selenium in global food systems. Br. J. Nutr. 85:517-547.[Medline]
42. Hawkes, W. C., Alkan, F. Z. & Oehler, L. (2003) Absorption, distribution and excretion of selenium from beef and rice in healthy North American men. J. Nutr. 133:3434-3442.
43. Van Loan, M. D., Keim, N. L. & Belko, A. Z. (1990) Body composition assessment of a general population using total body electrical conductivity (TOBEC). Hermans, G.P.H. Mosterd, W. I. eds. Sports, Medicine and Health, Excerpta Medica International Congress Series No. 921 1990 Elsevier Science Publishers Amsterdam, The Netherlands. .
44. Weir, J. B. (1949) New methods for calculating metabolic rate with special reference to protein metabolism. J. Physiol. 109:1-9.
45. Yang, G. Q., Qian, P. C., Zhu, L. Z., Huang, J. H., Liu, S. J., Lu, M. D. & Gu, L. Z. (1987) Human selenium requirements in China. Combs, G. F., Jr Levander, O. A. Spallholz, J. E. Oldfield, J. E. eds. Selenium in Biology and Medicine 1987 Van Norstrand Reinhold New York, NY. .
46. Levander, O. A. (1997) Selenium requirements as discussed in the 1996 joint FAO/IAEA/WHO expert consultation on trace elements in human nutrition. Biomed. Environ. Sci. 10:214-219.[Medline]
47. Longnecker, M. P., Taylor, P. R., Levander, O. A., Howe, S. M., Veillon, C., Mcadam, P. A., Patterson, K. Y., Holden, J. M., Stampfer, M. J. & Morris, J. S. (1991) Selenium in diet, blood and toenails in relation to human health in a seleniferous area. Am. J. Clin. Nutr. 53:1288-1294.
48. Kohrle, J. (1994) Thyroid hormone deiodination in target tissues—a regulatory role for the trace element selenium?. Exp. Clin. Endocrinol. 102:63-89.[Medline]
49. Kang, B. P., Bansal, M. P. & Mehta, U. (2000) Hyperlipidemia and type I 5'-monodeiodinase activity: regulation by selenium supplementation in rabbits. Biol. Trace Elem. Res. 77:231-239.[Medline]
50. Hotz, C. S., Fitzpatrick, D. W., Trick, K. D. & L’Abbé, M. R. (1997) Dietary iodine and selenium interact to affect thyroid hormone metabolism of rats. J. Nutr. 127:1214-1218.
51. Bratter, P. & Negretti de Bratter, V. E. (1996) Influence of high dietary selenium intake on the thyroid hormone level in human serum. J. Trace Elem. Med. Biol. 10:163-166.[Medline]
52. Calomme, M. R., Vanderpas, J. B., Francois, B., Van Caillie-Bertrand, M., Herchuelz, A., Vanovervelt, N., Van Hoorebeke, C. & Vanden Berghe, D. A. (1995) Thyroid function parameters during a selenium repletion/depletion study in phenylketonuric subjects. Experientia 51:1208-1215.[Medline]
53. Kauf, E., Dawczynski, H., Jahreis, G., Janitzky, E. & Winnefeld, K. (1994) Sodium selenite therapy and thyroid-hormone status in cystic fibrosis and congenital hypothyroidism. Biol. Trace. Elem. Res. 40:247-253.[Medline]
54. Olivieri, O., Girelli, D., Azzini, M., Stanzial, A. M., Russo, C., Ferroni, M. & Corrocher, R. (1995) Low selenium status in the elderly influences thyroid hormones. Clin. Sci. (Lond.) 89:637-642.[Medline]
55. Danforth, J., E., Horton, E. S., O’Connell, M., Sims, E.A.H., Burger, A. G., Ingbar, S. H., Braverman, L. & Vagenakis, A. G. (1979) Dietary-induced alterations in thyroid hormone metabolism during overnutrition. J. Clin. Investig. 64:1336-1347.
56. Hoogwerf, B. J. & Nuttall, F. Q. (1984) Long-term weight regulation in treated hyperthyroid and hypothyroid subjects. Am. J. Med. 76:963-970.[Medline]
57. Brent, G. A. (1994) The molecular basis of thyroid hormone action. N. Engl. J. Med. 331:847-853.
58. Wolman, S. L., Sheppard, H., Fern, M. & Waterlow, J. C. (1985) The effect of triiodothyronine (T3) on protein turnover and metabolic rate. Int. J. Obes. 9:459-463.[Medline]
59. Rozen, R., Abraham, G., Falcou, R. & Apfelbaum, M. (1986) Effects of a "physiological" dose of triiodothyronine on obese subjects during a protein-sparing diet. Int. J. Obes. 10:303-312.[Medline]
60. Finley, J. W. & Penland, J. G. (1998) Adequacy or deprivation of dietary selenium in healthy men: clinical and psychological findings. J. Trace Elem. Exp. Med. 11:11-27.
61. Benton, D. & Cook, R. (1991) The impact of selenium supplementation on mood. Biol. Psychiatry 29:1092-1098.[Medline]
62. Hawkes, W. C. & Hornbostel, L. (1996) Effects of dietary selenium on mood in healthy men living in a metabolic research unit. Biol. Psychiatry 39:121-128.[Medline]
63. Oppenheimer, J. H., Schwartz, H. L. & Strait, K. A. (1995) An integrated view of thyroid hormone actions in vivo. Weintraub, B. D. eds. Molecular Endocrinology: Basic Concepts and Clinical Correlations 1995 Raven Press New York, NY. .
64. Oppenheimer, J. H., Schwartz, H. L., Lane, J. T. & Thompson, M. P. (1991) Functional relationship of thyroid hormone-induced lipogenesis, lipolysis, and thermogenesis in the rat. J. Clin. Investig. 87:125-132.
65. Stevens, J., Knapp, R. G., Keil, J. E. & Verdugo, R. R. (1991) Changes in body weight and girths in black and white adults studied over a 25 year interval. Int. J. Obes. 15:803-808.[Medline]
66. Lewis, C. E., Smith, D. E., Wallace, D. D., Williams, O. D., Bild, D. E. & Jacobs, D. R., Jr (1997) Seven-year trends in body weight and associations with lifestyle and behavioral characteristics in black and white young adults: the CARDIA study. Am. J. Public Health 87:635-642.
67. Jeffery, R. W. & French, S. A. (1997) Preventing weight gain in adults: design, methods and one year results from the Pound of Prevention study. Int. J. Obes. Relat. Metab. Disord. 21:457-464.[Medline]
68. Clark, L. C., Combs, G. F., Jr, Turnbull, B. W., Slate, E. H., Chalker, D. K., Chow, J., Davis, L. S., Glover, R. A., Graham, G. F., Gross, E. G., Krongrad, A., Lesher, J. L., Jr, Park, H. K., Sanders, B. B., Jr, Smith, C. L. & Taylor, J. R. (1996) Effects of selenium supplementation for cancer prevention in patients with carcinoma of the skin. A randomized controlled trial. J. Am. Med. Assoc. 276:1957-1963.[Abstract]
69. Constans, J., Delmas-Beauvieux, M. C., Sergeant, C., Peuchant, E., Pellegrin, J. L., Pellegrin, I., Clerc, M., Fleury, H., Simonoff, M., Leng, B. & Conri, C. (1996) One-year antioxidant supplementation with beta-carotene or selenium for patients infected with human immunodeficiency virus: a pilot study. Clin. Infect. Dis. 23:654-656.[Medline]
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