Iodothyronine Deiodination Reaction Types in Several Rat Tissues: Effects of Age, Thyroid Status, and Glucocorticoid Treatment*

McCann, Una D.; Shaw, Elizabeth; Kaplan, Michael M.

doi:10.1210/endo-114-5-1513

Cited by 67 publications

(28 citation statements)

References 50 publications

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“…In P12 pups, however, DEX no longer affected circulating T 4 levels, whereas it significantly decreased plasma T 3 concentrations. Although previous experiments, using both adult and P7 rats, indicated that glucocorticoids reduced hepatic T 3 production (Jennings & Ferguson 1984, McCann et al 1984, our results suggested that in P12 rat pups the DEX-induced decrease in plasma T 3 levels is more likely due to the increased hepatic and possibly also renal T 3 degradation (via D3) without changes in peripheral T 3 production. A similar mechanism has been proposed to explain the glucocorticoid-induced decrease in plasma T 3 levels in man, although so far no direct experimental proof has been provided for this hypothesis (Chopra et al 1975, Westgren et al 1977, Lopresti et al 1989.…”

Section: Discussioncontrasting

confidence: 87%

Developmentally defined regulation of thyroid hormone metabolism by glucocorticoids in the rat

Geyten

Darras²

2005

Journal of Endocrinology

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Glucocorticoids are known regulators of thyroid function in vertebrates. In birds they have clear tissue-specific and age-dependent effects on thyroid hormone metabolism. In mammals, however, few studies exist addressing these aspects using an in vivo model system. We therefore set out to examine the acute effects of a single dose of dexamethasone (DEX) on plasma 3,5,3 -tri-iodothyronine (T 3 ) and thyroxine (T 4 ) levels, as well as on the activity of the different deiodinases in liver, kidney and brain in the developing rat. In 20-day-old fetuses (E20), glucocorticoids had no effects on circulating thyroid hormone levels despite their clear effects on hepatic and renal deiodinases, thereby indicating that under these conditions circulating thyroid hormone levels are more dependent on thyroidal secretion than on peripheral deiodination. In contrast, in 5-day-old rat pups, DEX did not seem to have any effects on hepatic and renal T 3 production (via the type I deiodinase), whereas type III deiodinase (D3) activity in both these tissues increased significantly. These observations therefore suggested that the DEX-induced increase in circulating T 3 levels is a direct consequence of the increase in plasma T 4 levels. In 12-day-old pups (P12), however, the main effect of glucocorticoids on circulating T 3 levels was by increasing inner ring deiodination through induction of D3 in both liver and kidney. Finally, in the brain, glucocorticoids stimulated thyroid hormone activity only during a short period of time (between E20 and P12) that largely overlaps with the transient window in time during which brain development is thyroid hormone sensitive. This was in contrast to the E20 and P12 brain, where the glucocorticoid-induced changes in type II deiodinase and D3 seemed to favor a status quo in local T 3 availability.

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Section: Discussioncontrasting

confidence: 87%

Developmentally defined regulation of thyroid hormone metabolism by glucocorticoids in the rat

Geyten

Darras²

2005

Journal of Endocrinology

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“…The finding by Osathanondh and colleagues of an increase in amniotic fluid rT3 levels in pregnant women administered DEX is consistent with this observation (35). However, McCann et al were unable to show any influence ofcorticosterone acetate on the type III 5-deiodinase system in rat liver in vitro (36). This may reflect either species variability or tissue specific regulation of type III 5-deiodinase enzyme activity.…”

Section: Resultsmentioning

confidence: 67%

Alterations in 3,3'5'-triiodothyronine metabolism in response to propylthiouracil, dexamethasone, and thyroxine administration in man.

LoPresti

Eigen²,

Kaptein³

et al. 1989

J. Clin. Invest.

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To elucidate the mechanisms involved in altering serum 3,3',5'-triiodothyronine (rT3) levels with absolute or relative low 3,5,3'-triiodothyronine (T3) states in man, agents capable of lowering circulating T3 levels were sequentially administered to six euthyroid subjects. These agents included propylthiouracil (PTU) (300 mg/6 h X 5 d), dexamethasone (DEX) (2 mg/6 h X 5 d), and thyroxine (T4) (3.0 mg load and 0.3 mg/d X 5 d). 1125I] rT3 clearance rates and rT3 production rates were then determined. Increased serum rT3 levels and rT3/T4 values occurred with both PTU and DEX as compared with control, while T4 increased serum rT3 but did so without changing rT3/T4 values. The rT3 clearance rate was significantly decreased by PTU without altering production rate, while DEX increased the rT3 production rate without altering the rT3 clearance rate. T4 administration did not change rT3 clearance but proportionately increased rT3 production. These responses indicate that circulating rT3 predominantly originates from a non-PTU inhibitable deiodinase enzyme system located in extrahepatic tissues. This enzyme system appears to have a high capacity and low affinity for T4 and can be stimulated by DEX administration.

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“…We describe the ontogenic pattern of fetal brain 5'D-I1 activity. A previous report using rT3 as substrate (34) found very low 5'D-I1 activity in 17-day-old fetal brain, with a 3-fold increase on the day of birth. Intermediate ages were not reported.…”

Section: Discussionmentioning

confidence: 71%

Developmental Changes in Rat Brain 5′-Deiodinase and Thyroid Hormones during the Fetal Period: The Effects of Fetal Hypothyroidism and Maternal Thyroid Hormones

Oña¹,

Obregón²,

Rey³

et al. 1988

Pediatr Res

109

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ABSTRACT. We have studied the ontogenesis of 5'-deiodinase (5'D) activity in rat brain during fetal life, its capacity to respond to maternal or fetal hypothyroidism, and its regulation by maternal thyroid hormones. Type I1 5'D (5' D-11) activity increases 4-fold during the period studied (17 to 22 days of gestation), mainly between days 19 and 21. Fetal brain T4 concentrations increase in parallel with fetal plasma T4, whereas fetal brain T3 concentrations increase 18 times (days 17-21), six times more than would have been expected from the small increase in fetal plasma T3 levels. Maternal thyroidectomy did not affect 5'D-I1 activity or thyroid hormone concentrations in fetal brain (except brain T4 at 18 days of gestation). Fetal hypothyroidism, induced by giving a goitrogen (methimazole) to the mothers, depleted all fetal tissues studied, including the fetal thyroid, from thyroid hormones. By 19 days of gestation, the fetal brain was able to respond to hypothyroidism with a 3-to 5-fold increase in 5'D-I1 activity. Earlier onset of treatment with methimazole led to 2-to 3-fold increases in 5'D already at 17 and 18 days of gestation, showing that when fetal thyroid secretion starts the fetal brain 5'D-I1 is able to respond to hypothyroidism. Replacement of methimazole-treated mothers with physiological doses of T4, given by constant infusion, increased T4 and T3 concentrations in fetal brain, and inhibited fetal, as well as maternal, brain 5'D-I1 activity. But treatment of the mothers with T3 did not change T3 concentrations in the fetal brain, despite the increase in fetal plasma T3, and actually increased 5'D-I1 in fetal brain. Maternal cerebral 5'D-I1 was not inhibited by T3 treatment. Inverse relationships were found between the 5'D-I1 and thyroid hormone concentrations in the fetal brain. These correlations were not identical for fetuses from thyroidectomized and control mothers. In fetuses from thyroidectomized dams, brain 5'D-I1 is more sensitive to a decrease in brain T4 than in the progeny of control

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Iodothyronine Deiodination Reaction Types in Several Rat Tissues: Effects of Age, Thyroid Status, and Glucocorticoid Treatment*

Cited by 67 publications

References 50 publications

Developmentally defined regulation of thyroid hormone metabolism by glucocorticoids in the rat

Developmentally defined regulation of thyroid hormone metabolism by glucocorticoids in the rat

Alterations in 3,3'5'-triiodothyronine metabolism in response to propylthiouracil, dexamethasone, and thyroxine administration in man.

Developmental Changes in Rat Brain 5′-Deiodinase and Thyroid Hormones during the Fetal Period: The Effects of Fetal Hypothyroidism and Maternal Thyroid Hormones

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