The Renal Clearance of Thyroid Hormones in the Isolated Perfused Rat Kidney

Adikofer, F; Hj, Schurek; Sörje, H.

doi:10.1055/s-2007-996301

Cited by 5 publications

(3 citation statements)

References 10 publications

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“…Only a minor fraction of T3 can be detected as T3S in the urine of adults and experimental animals (28,29). However, the amount of T3S in the glomerular filtrate could be greater than that found in the urine, due to re-absorbtion and subsequent deiodination of T3S at the tubular level, in a manner similar to that proposed for other iodothyronines (30). Indeed, kidney tissue exhibits high levels of type I MD activity, and the type I MD mRNA has been localized to the kidney proximal tubule (31).…”

Section: Discussionmentioning

confidence: 52%

Study of serum 3,5,3′-triiodothyronine sulfate concentration in patients with systemic non-thyroidal illness

Santini¹,

Chiovato²,

Bartalena³

et al. 1996

European Journal of Endocrinology

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Sulfation is an important pathway of triiodothyronine (T3) metabolism. Increased serum T3 sulfate (T3S) values have been observed during fetal life and in pathological conditions such as hyperthyroidism and selenium deficiency. Similar variations have also been reported in a small number of patients with systemic non-thyroidal illness, but the underlying mechanisms have not been elucidated. In this study, serum T3S concentrations have been measured by a specific radioimmunoassay in 28 patients with end-stage neoplastic disease (ESND) and in 44 patients with chronic renal failure (CRF); 41 normal subjects served as controls. Both ESND and CRF patients had lower serum total T4 (TT4) and total T3 (TT3) than normal controls, while serum reverse T3 (rT3) was increased significantly in ESND (0.7 +/- 0.5 nmol/l; p < 0.001 vs. controls) but not in CRF (0.3 +/- 0.1 nmol/l). The TT3/rT3 ratio, an index of type I iodothyronine monodeiodinase (type I MD) activity, was reduced significantly in both groups of patients. Serum T4-binding globulin (TBG) was decreased in CRF but not in ESND patients. Serum T3S was significantly higher both in ESND (71 +/- 32 pmol/l) and CRF (100 +/- 24 pmol/l) than in controls (50 +/- 16 pmol/l, p < 0.001). Serum T3S values showed a positive correlation with rT3 values and a negative correlation with both TT3 and FT3 values in ESND, but not in CRF. In the latter group a positive correlation was observed between T3S and TBG values. The T3S/FT3 ratio was higher both in CRF (18 +/- 5) and in ESND (23 +/- 18) as compared to controls (10 +/- 4). Serum inorganic sulfate was increased and correlated positively with T3S values in CRF patients. In conclusion, the results of this study in a large series of patients confirm that patients with systemic non-thyroidal illness have increased serum T3S levels. The mechanisms responsible for these changes appear to be different in ESND and CRF patients. In ESND the increase in serum T3S levels is mainly related to reduced degradation of the hormone by type I MD, whereas in CRF it might be driven by the enhanced sulfate ion concentration, and could be partially dependent on the impaired renal excretion of T3S. Because T3S can be reconverted to T3, it is possible that increased T3S concentrations contribute to maintenance of the euthyroid state in systemic non-thyroidal disease.

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Section: Discussionmentioning

confidence: 52%

Study of serum 3,5,3′-triiodothyronine sulfate concentration in patients with systemic non-thyroidal illness

Santini¹,

Chiovato²,

Bartalena³

et al. 1996

European Journal of Endocrinology

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“…These findings are in agreement with the hormone analogue studies reported here which support a role of the brush border membrane in reduc ing the ability of 0-T 3 and Triac to reach the nucleus of renal cells. Clearance studies have established the existence of a high-capacity reabsorptive system for T 3 and T 4 in the rat [ 12] and for T 4 in euthyroid humans [43,44], Thus, the presence of specific binding sites for T 3 on the luminal membrane supports the possibility that these sites may be, somehow, involved in the reabsorption of thyroid hor mones. If this hypothesis is correct, and given the low affinities of £>-T3, D-T4 and Triac for the luminal binding sites, the tubular reab sorption of these analogues should be very low.…”

Section: Discussionmentioning

confidence: 94%

“…Conversely, there is evi dence that receptor-mediated endocytosis is one mechanism for T 3 entry into cultured mouse fibroblasts [5,7,8], GH3 cells [9] and rat skeletal myoblasts [ 10], Unexpectedly, in view of the potential im portance o f the kidney in the homeostatic reg ulation of T 3 and T 4 in the body fluids, the renal handling of these hormones is largely unknown. Studies in the isolated perfused rat kidney [ 11,12] have suggested that reabsorp tion of T 3 and T4 occurs by means of a highcapacity transport system. However, experi ments in the rat equilibrated with either [125I]-labeled T 3 or 3.3',5-triiodo-J9-thyronine (D-T 3) have suggested that transport of D-T 3 from plasma to cytosol in kidney occurs by an energy-dependent stereospecific process, whereas transmembrane T 3 transport is by simple diffusion [13].…”

Section: Introductionmentioning

confidence: 99%

Stereospecific Triiodothyronine Binding Sites in Rabbit Renal Apical Membranes and Their Functional Role in the Proximal Tubule

Chambrey¹,

Podevin²

1992

Cell Physiol Biochem

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In mammals, L-thyroxine (T₄) and 3,3’,5-L-triiodothyronine (T₃) are reabsorbed by a tubular transport mechanism of high capacity. We investigated the first step of this reabsorptive process. In experiments using rabbit renal apical membrane vesicles, measurements of [¹²⁵I] T₃ uptake at steady state indicated that uptake represented mainly membrane binding. Luminal binding sites showed equal affinity for T₃ and T₄, whereas their nonphysiological D-forms have only a 10% effectiveness in competing with T₃. The presence of a Na⁺ or a H⁺ symport pathway for T₃ in these vesicles could not be demonstrated. Incubation of freshly isolated proximal tubules in hyperosmolar medium, a maneuver known to inhibit endocytosis, led to rapid (2 min) inhibition of specific T₃ uptake. This effect was associated with a decrease in enriched intracellular membrane fractions in the levels of leucine aminopeptidase, a luminal marker, but with no change in the levels of Na/K ATPase, a basolateral marker, suggesting that hyperosmolarity reduces internalization of the apical membrane domain. These findings suggest that receptor-mediated endocytosis may be one pathway for the initial step in thyroid hormone reabsorption by the proximal tubule.

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Regulation of conversion of thyroxine to triiodothyronine in perfused rat kidney

Ferguson

Jennings

1983

American Journal of Physiology-Endocrinology and Metabolism

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The factors regulating the renal uptake of thyroxine (T4), its conversion to 3,5,3'-triiodothyronine (T3), and the urinary iodothyronine excretion were studied in the perfused rat kidney. Increasing the perfusate free T4 (FT4) concentration from 1 to 11.5 times that of euthyroid rat serum resulted in a linear increase in T4 uptake and T3 production that was not saturated at the highest dose. When FT4 concentrations were increased by decreasing the perfusate albumin concentration from 7.5 to 2.5 g/dl, T4 uptake and T3 production increased in proportion to the FT4 concentration. Propylthiouracil (PTU), a 5'-deiodinase inhibitor, decreased renal T3 production by 60.5% without affecting tissue T4 uptake. In the absence of glomerular filtration, T4 uptake and T3 production were unchanged, indicating that T4 is extracted by the contraluminal surface of the renal tubule. However, probenecid, an inhibitor of contraluminal organic acid uptake, did not decrease but increased T4 uptake and T3 production by increasing the perfusate FT4 fraction in the perfusate. There was no net renal 3,3',5'-triiodothyronine (rT3) production from T4, and degradation and urinary excretion of T3 were negligible. The urinary excretion of T4 and T3 correlated closely with the degree of proteinuria.

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The Renal Clearance of Thyroid Hormones in the Isolated Perfused Rat Kidney

Cited by 5 publications

References 10 publications

Study of serum 3,5,3′-triiodothyronine sulfate concentration in patients with systemic non-thyroidal illness

Study of serum 3,5,3′-triiodothyronine sulfate concentration in patients with systemic non-thyroidal illness

Stereospecific Triiodothyronine Binding Sites in Rabbit Renal Apical Membranes and Their Functional Role in the Proximal Tubule

Regulation of conversion of thyroxine to triiodothyronine in perfused rat kidney

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