The Formation of Tri-Iodothyronine and Reverse Triiodothyronine from Thyroxine in Isolated Rat Renal Tubules

Heyma, Paula; Larkins, R. G.; Stockigt, Jan R.; Campbell, D. J.

doi:10.1042/cs0550567

Cited by 13 publications

(9 citation statements)

References 18 publications

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“…The inhibitory effect of PTU on rT3 degradation in vivo is in good agreement with observations in studies on iodothyronine degradation in vitro (Kaplan & Utiger, 1978;Chopra et al, 1978;Heyma et al, 1978). In rat liver homogenate PTU inhibits T4 monodeiodination to rT3 (Cavalieri et a/., 1977).…”

Section: Discussionsupporting

confidence: 81%

DYNAMICS OF SERUM rT3 AND 3, 3‐T2 DURING rT3 INFUSION IN PATIENTS TREATED FOR THYROTOXICOSIS WITH PROPYLTHIOURACIL OR METHIMAZOLE

Laurberg

Weeke

1980

Clinical Endocrinology

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rT3 metabolism in patients treated for thyrotoxicosis with prophylthiouracil (PTU), or methimazole (MMI) was studied by infusion of rT3 and measurements of the increase in serum rT3 and serum 3,3'-diiodothyronine. The results indicate that the high serum rT3 observed during treatment with PTU is not due to an increase in rT3 production, but to a decrease in the metabolic clearance rate of rT3. rT3 infusion was followed by an increase in serum 3,3'-T2 which was similar whether PTU or MMI was given. However, after stopping rT3 infusion there was a more rapid fall serum 3,3'-T2 during MMI treatment, compatible with an inhibitory effect of PTU on 3,3'-T2 degradation.

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Section: Discussionsupporting

confidence: 81%

DYNAMICS OF SERUM rT3 AND 3, 3‐T2 DURING rT3 INFUSION IN PATIENTS TREATED FOR THYROTOXICOSIS WITH PROPYLTHIOURACIL OR METHIMAZOLE

Laurberg

Weeke

1980

Clinical Endocrinology

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“…This is somewhat in conflict with previous studies by Hesch et al (1975) who found T3 confined to the intracellular space in suspen¬ sions of rat hepatocytes after 60 min incubation, and Heyma et al (1978) who studied the T4 to T3 conversion in isolated rat renal tubules and found that the intracellular concentration of T3 was five times greater than in the medium after 60 min incubation. In our study the intra-and extracellu¬ lar concentrations of T3 seem to have reached an equilibrium state after 120 min incubation, which may imply efflux of T3 across the plasma mem¬ brane.…”

Section: Discussioncontrasting

confidence: 74%

Metabolism of thyroid hormones in isolated rat hepatocytes: studies on the influences of carbamazepine and phenytoin

Aanderud

Aarbakke

Sundsfjord

1983

Acta Endocrinologica

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The in vitro handling of thyroid hormones was studied in isolated rat hepatocytes by measuring 1) the cellular uptake of T4, 2) the conversion of T4 to T3 and 3) the degradation of T4 and T3. The in vitro conversion of T4 to T3 increased significantly by adding ethanol 2% or carbamazepine (CBZ) 400 \g=m\m in ethanol 2% to the incubation medium. As there was no difference between ethanol and CBZ/ethanol on the T3 formation, this effect was probably caused by ethanol. The T3 formation was unaffected by phenytoin (PHT) in conc. up to 400 \g=m\m, while propylthiouracil (PTU) 100 and 400 \g=m\minhibited the conversion completely. The T4 to T3 conversion in hepatocytes from rats pretreated with CBZ or PHT for 2 weeks was not significantly different from untreated controls. The cellular uptake of T4 was reduced by about 30% in the presence of PHT and unaltered by CBZ and ethanol. The degradation of T4 and T3 was not influenced by the in vitro addition of CBZ or PHT, nor was the degradation of T4 and T3 significantly different from untreated controls in hepatocyte suspensions from CBZ or PHT pretreated rats. Our findings suggest that the handling of thyroid hormones in isolated rat hepatocytes is not influenced by the in vitro or in vivo exposure to CBZ or PHT.Decreased serum levels of thyroxine (T4) and triiodothyronine (T3) have been reported during treat¬ ment of epilepsy with phenytoin (PHT) and car¬ bamazepine (CBZ) (M0lholm Hansen et al. 1974; Fichsel & Kn0pfle 1978; Liewendahl et al. 1978; Rootwelt et al. 1978; Cavalieri et al. 1979; Strandjord et al. 1981). Drug induced increase in the metabolism of T4 and T3 has been proposed (Mendoza et al. 1966; Liewendahl et al. 1980; Aanderud et al. 1981), but the mechanism(s) behind the changes in thyroid hormone levels are still unknown. The major source of T3 is the extrathyroidal deiodination of T4 (for review, see Schimmel &Utiger 1977). T4 to T3 conversion has been repor¬ ted to occur in various mammalian tissues inclu¬ ding liver and kidney (Chopra 1977;Kaplan et al. 1979). The liver deiodination is probably most important as the liver accounts for more than 80% of the total cellular distribution of T4 (Oppenheimer et al. 1967), and has a high T4 to T3 converting activity (Kaplan et al. 1979). The in vivo conversion of T4 to T3 is influenced by several factors such as the nutritional state, non-thyroidal illness and several pharmacological agents (Schim¬ mel & Utiger 1977;Cavalieri & Pitt-Rivers 1981).Drugs may change the peripheral metabolism of thyroid hormones by interfering with 1) the cellu¬ lar uptake of T4, 2) the deiodination of T4 to T3, and 3) the degradation of T4 and T3. The present study was performed in order to determine the in vitro effect of PHT and CBZ on these variables, using suspensions of isolated rat hepatocytes. In order to study possible long-term effects of the drugs or metabolites, the handling of thyroid hor¬ mones was also studied in suspensions of hepato¬ cytes from rats pretreated with PHT or CBZ for 2 weeks. Materials and Methods Chemi...

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“…In our study, iodine inhibited the in vitro formation of T 3 by about 10%. Previous in vivo and in vitro studies were, however, unable to demonstrate any effect of iodine on the extrathyroid metabolism of thyroid hormones (6,16,17). The demonstrated effect of iodine on the in vitro conversion of T 4 to T 3 was negligible compared with that of amiodarone at concentrations containing isomolar amounts of iodine, suggesting that the total blockade of the T 3 formation by 60 /iM amiodarone was essentially unrelated to a possible release of iodide.…”

Section: Discussionmentioning

confidence: 46%

Amiodarone Inhibits the Conversion of Thyroxine to Triiodothyronine in Isolated Rat Hepatocytes

1984

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Previous studies have shown decreased T3 and increased T4 and rT3 serum levels in subjects treated with amiodarone. We studied the acute effect of amiodarone on the in vitro conversion of T4 to T3 in suspensions of isolated rat hepatocytes. Iodine and melperone, another class III antiarrhythmic drug, were included in the study as controls. Amiodarone (60 microM) totally blocked the formation of T3 from T4, whereas concentrations of 6 and 0.6 microM reduced T3 formation to 13.7 +/- 10.6% and 63.9 +/- 15.9% (+/- SD), respectively, compared with untreated controls. The drug solvent did not affect the conversion rate. Iodide (120 microM) had an inhibitory effect of approximately 10% compared with the controls, whereas melperone did not affect this in vitro conversion. Amiodarone (60 microM) caused a slight but significant reduction of the cellular uptake of [125I]T4 after 10 min of incubation, whereas the 60 min values were unaltered. Our study indicates that amiodarone inhibits the 5'-monodeiodination of T4 to T3 in a dose-related manner. It is suggested that the antiarrhythmic activity of the drug is related to its inhibitory effect on the conversion of T4 to T3.

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The Formation of Tri-Iodothyronine and Reverse Triiodothyronine from Thyroxine in Isolated Rat Renal Tubules

Cited by 13 publications

References 18 publications

DYNAMICS OF SERUM rT3 AND 3, 3‐T2 DURING rT3 INFUSION IN PATIENTS TREATED FOR THYROTOXICOSIS WITH PROPYLTHIOURACIL OR METHIMAZOLE

DYNAMICS OF SERUM rT3 AND 3, 3‐T2 DURING rT3 INFUSION IN PATIENTS TREATED FOR THYROTOXICOSIS WITH PROPYLTHIOURACIL OR METHIMAZOLE

Metabolism of thyroid hormones in isolated rat hepatocytes: studies on the influences of carbamazepine and phenytoin

Amiodarone Inhibits the Conversion of Thyroxine to Triiodothyronine in Isolated Rat Hepatocytes

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