Effects of selenium deficiency on thyroid hormone economy in rats.

Abstract

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.

Serum iodothyronine concentrations in intestinally decontaminated rats treated with a 5′-deiodinase type I inhibitor 6-anilino-2-thiouracil

“…Intrathyroidal 5'D-I deiodination of T4 to generate T3 does not appear to be a major source of circulating T3, because serum T3 concentrations were not decreased in the ATU-treated rats despite a 60% reduction in 5'D-I activity. However, Laurberg has reported that intrathyroid deiodination of T4 to T3 accounts for a considerable portion of the T3 secreted from the dog thyroid (26, 27) and we have also suggested that this pathway of T3 generation in the thyroid appears to be important in the rat (23).…”

“…It has been shown previously that a marked decrease in 5'D-I activity in the liver and kidney by more than 90% in selenium-deficient intact rats was associated with only a modest or no decrease in the serum T3 concentration (20)(21)(22). fn addition, in selenium-deficient, thyroidectomized, T4-replaced rats the serum T3 concentration was only decreased by 20% as compared to selenium-supplemented, thyroidecto¬ mized, T4-replaced rats (23). These data are consistent with the finding that in mice lacking 5'D-I, the serum T3 concentration is normal (24,25).…”

Selective macrophage depletion in the liver does not prevent the development of the sick euthyroid syndrome in the mouse

“…We therefore looked for the effect of reduced food intake in a separate experiment, and showed that the decrease in serum T3 and T4 after 24-h starvation was not affected by depleting the liver of Kupffer cells. Considering that considerable amounts of T3 are produced from deiodination of T4 in the thyroid, which appears to be an important source of T3 production in rats (36), it might be plausible that decreased levels of thyroidal 5'-deiodinase contribution to the observed LPS-induced decrease of serum T3. This is in agreement with the results of O'Mara et al, who found only a significant decrease in 5'-deiodinase mRNA in rats after 48-h starvation but not after 24 h, while serum T3 was already signifi¬ cantly decreased (34).…”

Selenium and thyroid function in infants, children and adolescents

“…These observations are consistent with data obtained from animal studies. Prolonged, isolated selenium deficiency in rodents causes an almost complete loss in liver 5 DI activity and an increase in circulating T 4 [23] and T 4 half-life with no [11,23] or little [10,24] changes in T 3 or TSH concentrations. Interestingly, selenium deficiency is associated with an increase in serum rT 3 concentrations in young rats [25] but not in adult male [9,10] or non-pregnant female rats [26].…”

“…5 DI contains the rare aminoacid selenocysteine [8] and tissue content of 5 DI is proportional to selenium intake. In rodents, severe selenium deficiency causes a marked decrease in liver and kidney 5 DI activities [9][10][11]. The other isozyme, type II 5 -deiodinase (5 DII), is abundant in human brain, heart, skeletal muscle [12], pituitary tumors [13] and thyroid [12,14] (rev in [7]).…”