Regulation of thyroid hormone metabolism in rat liver fractions

Höffken, B.; Ködding, R.; Mühlen, A. von zur; Hehrmann, Tainer; Jüppner, Harald; Hesch, R. D.

doi:10.1016/0304-4165(78)90126-5

Cited by 21 publications

(7 citation statements)

References 41 publications

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“…Previous studies have shown that various mercaptans stimulate the T3-neogenesis in liver homogenates (41) and microsomes (42)(43)(44). Therefore, experiments were performed to assess the effect of GSH in microsomes incubated in buffer or in cytosols obtained from either fed or fasted rats (Table IV).…”

Section: Resultsmentioning

confidence: 99%

“…Specifically, we have examined the activity of crude microsomal preparations, in which the 5'-monodeiodinating enzyme is thought to reside (42,43) and have studied the influence thereon of hepatic cytosol, a subcellular fraction virtually devoid ofintrinsic deiodinase activity. Our observations are consonant with others that indicate that crude microsomal preparation is richest in 5'-monodeiodination for T4 (42)(43)(44), because under any given condition this fraction was more active on a unit protein basis than nuclear, mitochondrial, or cytosolic fractions were (data not shown). Distinct, though low, activity was present in microsomes incubated in buffer, because values for T3 generation, though small, consistently exceeded those found in tissue-free or unincubated controls.…”

Section: Resultsmentioning

confidence: 99%

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Observations on the factors that control the generation of triiodothyronine from thyroxine in rat liver and the nature of the defect induced by fasting.

Balsam¹,

Ingbar²

1979

J. Clin. Invest.

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A B S T R A C T Studies were performed to explore the mechanism underlying the impaired generation of 125-I-3,5,3'-triiodothyronine (T3) from 1251-thyroxine (T4) (T3-neogenesis) in preparations of liver from rats fasted for 48 h and the prevention of this effect by the feeding of glucose. T3-neogenesis in livers from fasted animals and those fed chow or glucose was assessed in various mixtures of crude microsomal fractions with either buffer or cytosols. T3-neogenesis was mediated by an enzyme present in the microsomal fraction whose activity was enhanced by cytosolic cofactor(s). In livers from animals fasted for 48 h, the supporting activity of cytosol was decreased, whereas the activity of the enzyme was unaffected. Administration of glucose as the sole nutritional source prevented the decrease in the supporting activity of hepatic cytosol that was regularly observed in the case of animals totally deprived of food.The diminished supporting activity for T3-neogenesis provided by liver cytosol from fasted animals was restored to normal by enrichment with either NADPH or GSH, but the two cofactors appeared to act at different loci. GSH stimulated T3-neogenesis in microsomes incubated in the absence of cytosol, i.e., in buffer, whereas NADPH did not. The stimulatory effect of both agents was blocked by the sulfhydryl oxidant, diamide, which also inhibited T3-neogenesis in mixtures of microsomes with cytosols. Taken together, these observations suggest that GSH acts directly on the enzyme in the crude microsomal fraction, whereas NADPH acts within the cytosol, possibly by increasing the concentration of GSH through the action of the enzyme glutathione reductase, for which NADPH is a cofactor. In this light, the decreased supporting activity of hepatic cytosol

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Observations on the factors that control the generation of triiodothyronine from thyroxine in rat liver and the nature of the defect induced by fasting.

Balsam¹,

Ingbar²

1979

J. Clin. Invest.

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“…The conclusive demonstration of in vivo peripheral conversion of T4 to T3 in man (1) revived interest in various aspects of the peripheral metabolism of T4. Many workers have demonstrated that different tissues actively deiodinate T4 to T3 (19)(20)(21)(22)(23)(24), but liver and kidney are the most active (25)(26)(27)(28)(29)(30)(31)(32)(33). The conversion is enzymatic, because it is temperature, pH, and substrate concentration dependent (29)(30)(31)(32)(33).…”

Section: Introductionmentioning

confidence: 99%

“…Many workers have demonstrated that different tissues actively deiodinate T4 to T3 (19)(20)(21)(22)(23)(24), but liver and kidney are the most active (25)(26)(27)(28)(29)(30)(31)(32)(33). The conversion is enzymatic, because it is temperature, pH, and substrate concentration dependent (29)(30)(31)(32)(33). Compounds such as iopanoic acid, propylthiouracil, and rT3 have been demonstrated to be potent inhibitors of T4 to T3 conversion in vitro (29,33,34) and in vivo (35)(36)(37).…”

Section: Introductionmentioning

confidence: 99%

“…The conversion is enzymatic, because it is temperature, pH, and substrate concentration dependent (29)(30)(31)(32)(33). Compounds such as iopanoic acid, propylthiouracil, and rT3 have been demonstrated to be potent inhibitors of T4 to T3 conversion in vitro (29,33,34) and in vivo (35)(36)(37). Visser et al (38) first reported the importance of sulfhydryl groups in the conversion of T4 to T3 because thiol protective agents such as glutathione or dithiothreitol (DTT) added in vitro enhanced 5'-deiodinating enzyme activity, whereas thiol oxidizing agents abolished it.…”

Section: Introductionmentioning

confidence: 99%

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The Role of Sulfhydryl Groups on the Impaired Hepatic 3′,3,5-Triiodothyronine Generation from Thyroxine in the Hypothyroid, Starved, Fetal, and Neonatal Rodent

Harris¹,

Fang²,

Hinerfeld³

et al. 1979

J. Clin. Invest.

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A B S T R A C T The role of nonprotein sulflhydryl groups (NPSH) in the decreased in vitro hepatic 3',3,5-triiodothyronine (T3) generation from thyroxine (T4) in the starved, hypothyroid, fetal and 1-to 4-d-old neonatal rat and dwarf mouse was assessed. NPSH were measured in fresh 25% liver homogenates prepared in 0.1 M P04/10 mM EDTA buffer. As 516 4-d-old neonates, but had little or no effect in the fetal and hypothyroid rat and dwarf mouse. Liver homogenates stored for 6 mo at -20°C lost their capacity to generate T3 from T4. NPSH concentrations in the frozen homogenates decreased progressively with increasing storage and were absent by 6 mo. 5'-Deiodinase activity correlated with NPSH concentration in the stored homogenates (r = 0.95, P < 0.005). Addition of DTT partially restored hepatic T3 generation in the frozen homogenate. It is concluded that NPSH are important for the action of the liver 5'-deiodinase. The decreased hepatic T3 generation in the starved rat is associated with decreased NPSH but not with a decrease in the absolute quantity of 5'-deiodinase because provision of sulfhydryl groups restored hepatic T3 generation to normal. In contrast, the decreased hepatic T3 generation in the adult hypothyroid rodent and in the fetal rat is probably due to a decrease in the enzyme concentration per se. In the 1-and 4-d neonatal rat, the decrease in hepatic T3 generation is secondary to a decrease in NPSH and the deiodinating enzyme.

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Serum thyroid hormone levels in patients with fulminant hepatitis: Usefulness of rT3 and the rT3/T3 ratio as prognostic indices

et al. 1987

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To evaluate thyroid function in 19 patients with fulminant hepatitis (FH), we have measured total and free 3,5,3'-triiodothyronine (T3) and thyroxine (T4), 3,3',5'-triiodothyronine (reverse T3, rT3), thyroid-stimulating hormone (TSH) and thyroxin-binding globulin (TBG) in patients with FH, compared with those of 80 patients with other various liver diseases and of 10 healthy controls. Patients with FH showed the lowest values of serum T3 and the highest levels of rT3 among all patients with liver diseases studied. Furthermore, patients with FH showed a significant increase of rT3 in comparison with subacute hepatitis (SAH), "acute-on-chronic" (AOC) type of hepatic failure, ordinary and severe forms of acute hepatitis (AHo and AHs) and decompensated liver cirrhosis (LC-D). In addition, serum T3 and rT3 and the rT3/T3 ratio significantly correlated with prothrombin time (PT) and plasma methionine level. We also found that serum T3 and rT3 concentrations and the rT3/T3 ratio showed early and rapid normalization in cases of FH that survived, but they did not improve in patients with fatal outcome. These results suggest that serum T3, particularly rT3 concentrations and the rT3/T3 ratio may be useful indicators for assessing the severity and prognosis of patients with FH and can be considered to the sensitive indices for functioning hepatic microsomal reserve as well.

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Regulation of thyroid hormone metabolism in rat liver fractions

Cited by 21 publications

References 41 publications

Observations on the factors that control the generation of triiodothyronine from thyroxine in rat liver and the nature of the defect induced by fasting.

Observations on the factors that control the generation of triiodothyronine from thyroxine in rat liver and the nature of the defect induced by fasting.

The Role of Sulfhydryl Groups on the Impaired Hepatic 3′,3,5-Triiodothyronine Generation from Thyroxine in the Hypothyroid, Starved, Fetal, and Neonatal Rodent

Serum thyroid hormone levels in patients with fulminant hepatitis: Usefulness of rT3 and the rT3/T3 ratio as prognostic indices

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