Characteristics of active transport of thyroid hormone into rat hepatocytes

Krenning, Eric P.; Docter, R.; Bernard, Bert F.; Visser, Theo J.; Hennemann, G

doi:10.1016/0304-4165(81)90165-3

Cited by 119 publications

(78 citation statements)

References 14 publications

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“…However, the rT3 levels in the culture medium are largely protein bound and certainly do not reflect intracellularly available substrate concentrations. Together with the uncertainty about the saturation kinetics ofthe type I deiodinase in its natural environment it is, therefore, impossible to interpret these findings in terms of a possible uphill gradient of rT3 across the cell membrane (38).…”

Section: Resultsmentioning

confidence: 99%

Metabolism of reverse triiodothyronine by isolated rat hepatocytes.

Rooda¹,

Loon²,

Tj³

1987

J. Clin. Invest.

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Reverse triiodothyronine (rT3) is metabolized predominantly by outer ring deiodination to 3,3'-diiodothyronine (3,3'-T2) in the liver. Metabolism of rT3 and 3,3'-T2 by isolated rat hepatocytes was analyzed by Sephadex LH-20 chromatography, high performance liquid chromatography, and radioimmunoassay, with closely agreeing results. Deiodinase activity was inhibited with propylthiouracil (PTU) and sulfotransferase activity by sulfate depletion or addition of salicylamide or dichloronitrophenol. Normally, little 3,3'-T2 production from rT3 was observed, and 1251 was the main product of both 3,13'-'25iT2 and 13',5'-25IlrT3. PTU inhibited rT3 metabolism but did not affect 3,3'-T2 clearance as explained by accumulation of 3,3'-T2 sulfate. Inhibition of sulfation did not affect rT3 clearance but 3,3'-T2 metabolism was greatly diminished. The decrease in I formation from rT3 was compensated by an increased recovery of 3,3'-T2 up to 70% of rT3 metabolized. In conclusion, significant production of 3,3'-T2 from rT3 by rat hepatocytes is only observed if further sulfation is inhibited.

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Section: Resultsmentioning

confidence: 99%

Metabolism of reverse triiodothyronine by isolated rat hepatocytes.

Rooda¹,

Loon²,

Tj³

1987

J. Clin. Invest.

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“…In liver, T 3 and T 4 uptake has been reported to be mediated by different transporters (Krenning et al 1981), or the same carrier system (Blondeau et al 1988). In rat anterior pituitary cells, rT 3 , T 4 and T 3 share the same transporter (Everts et al 1994), while in rat hepatocytes rT 3 and T 4 share the same transporter, which is different from that for T 3 (Krenning et al 1982).…”

Section: Discussionmentioning

confidence: 99%

Comparison of mechanisms mediating uptake and efflux of thyroid hormones in the human choriocarcinoma cell line, JAR

Mitchell¹,

Rowan²,

Manley³

et al. 1999

Journal of Endocrinology

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We compared the specificities of transport mechanisms for uptake and efflux of thyroid hormones in cells of the human choriocarcinoma cell line, JAR, to determine whether triiodothyronine (T 3 ), thyroxine (T 4 ) and reverse T 3 (rT 3 ) are carried by the same transport mechanism. Uptake of 125 I-T 3 , 125 I-T 4 and 125 I-rT 3 was saturable and stereospecific, but not specific for T 3 , T 4 and rT 3 , as unlabelled -stereoisomers of the thyroid hormones inhibited uptake of each of the radiolabelled hormones. Efflux of 125 I-T 3 was also saturable and stereospecific and was inhibited by T 4 and rT 3 . Efflux of 125 I-T 4 or 125 I-rT 3 was, in contrast, not significantly inhibited by any of the unlabelled thyroid hormones tested. A range of compounds known to interfere with receptor-mediated thyroid hormone uptake in cells inhibited uptake of 125 I-T 3 and 125 I-rT 3 , but not 125 I-T 4 . We conclude that in JAR cells uptake and efflux of 125 I-T 3 are mediated by saturable and stereospecific membrane transport processes. In contrast, the uptake, but not the efflux, of 125 I-T 4 and 125 I-rT 3 is saturable and stereospecific, indicating that uptake and efflux of T 4 and rT 3 in JAR cells occur by different mechanisms. These results suggest that in JAR cells thyroid hormones may be transported by at least two types of transporters: a low affinity iodothyronine transporter (Michaelis constant, K m , around 1 µM) which interacts with T 3 , T 4 and rT 3 , but not amino acids, and an amino acid transporter which takes up T 3 , but not T 4 or rT 3 . Efflux of T 4 and rT 3 appears to occur by passive diffusion in these cells.

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“…Studies with cultured anterior pituitary cells also suggested a common carrier for uptake of T 3 and T 4 (Everts et al 1994). This is different from the situation in the liver, where separate carriers are presumably involved in uptake of T 3 and T 4 (Krenning et al 1981). These differences suggest that thyroid hormone uptake is regulated in a tissue-specific manner, which may significantly influence total thyroid hormone bioactivity (Everts et al 1996a, Hennemann et al 1998, 2001).…”

Section: Discussionmentioning

confidence: 84%

“…Whereas carrier-mediated uptake of T 3 has been demonstrated in various tissues (Kragie 1994, evidence for an active transport mechanism for T 4 is not as abundant. T 4 uptake has been explored in hepatocytes (Krenning et al 1981), anterior pituitary cells (Everts et al 1994), neuroblastoma cells (Lakshmanan et al 1990), fibroblasts (Docter et al 1987, Benvenga & Robbins 1990) and skeletal muscle (van Hardeveld & Kassenaar 1978). T 4 uptake in these cell types is mediated by a saturable and energy-dependent mechanism.…”

Section: Discussionmentioning

confidence: 99%

Uptake of tri-iodothyronine and thyroxine in myoblasts and myotubes of the embryonic heart cell line H9c2(2-1)

Putten

Joosten²,

Klaren³

et al. 2002

Journal of Endocrinology

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Uptake of tri-iodothyronine (T 3 ) was compared with that of thyroxine (T 4 ) in the embryonic heart cell line H9c2 (2-1). These cells propagate as myoblasts and form differentiated myotubes upon reduction of the serum concentration, as indicated by a 31-fold increase in creatine kinase activity. Protein and DNA content per well were around 2-fold higher in myotubes than in myoblasts. When expressed per well, T 3 and T 4 uptake were, compared with myoblasts, 1·9-to 2-fold and 3·1-to 4-fold higher in myotubes respectively. On the other hand, the characteristics of T 3 and T 4 uptake were similar in myoblasts and myotubes. At any time-point, T 4 uptake was 2-fold higher than that of T 3 , and both uptakes were energy but not Na + dependent. T 3 and T 4 uptake exhibited mutual inhibition in myoblasts and myotubes: 10 µM unlabeled T 3 reduced T 4 uptake by 51-60% (P<0·001), while 10 µM T 4 inhibited T 3 uptake by 48-51% (P<0·001). Furthermore, T 3 and T 4 uptake in myoblasts was dose-dependently inhibited by tryptophan (maximum inhibition around 70%; P<0·001). Exposure of the cells to T 3 or T 4 during differentiation significantly increased the fusion index (35 and 40%; P<0·01). Finally, both myoblasts and myotubes showed a small deiodinase type I activity, while deiodinase type II activity was undetectable. In conclusion, T 3 and T 4 share a common energy-dependent transport system in H9c2(2-1) cells, that may be important for the availability of thyroid hormone during differentiation.

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Characteristics of active transport of thyroid hormone into rat hepatocytes

Cited by 119 publications

References 14 publications

Metabolism of reverse triiodothyronine by isolated rat hepatocytes.

Metabolism of reverse triiodothyronine by isolated rat hepatocytes.

Comparison of mechanisms mediating uptake and efflux of thyroid hormones in the human choriocarcinoma cell line, JAR

Uptake of tri-iodothyronine and thyroxine in myoblasts and myotubes of the embryonic heart cell line H9c2(2-1)

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