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Biomedical subjects

G Hennemann

Publications and source records attributed to G Hennemann.

At least 37 records · Page 2Linked to original sources
PubMed1996

Effects of interleukin-1 beta on thyrotropin secretion and thyroid hormone uptake in cultured rat anterior pituitary cells.

The effects of interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF alpha) on basal and TRH-induced TSH release, and the effects of IL-1 beta on the uptake of [125I]T3 and [125I]T4 and on nuclear binding of [125I]T3 were examined. Furthermore, the release of other anterior pituitary hormones in the presence of IL-1 beta was measured. Anterior pituitary cells from male Wistar rats were cultured for 3 days in medium containing 10% FCS. Incubation were performed at 37 C in medium with 0.5% BSA for measurement of [125I]T3 uptake and with 0.1% BSA for measurement of [125I]T4 uptake. Exposure to IL-1 beta (1 pM-1 nM) or TNF alpha (100 pM) for 2-4 h resulted in a significant decline in TSH release, which was almost 50% (P < 0.05) for 1 nM IL-1 beta and 24% (P < 0.05) for 100 pM TNF alpha. Measurement of other anterior pituitary hormones (FSH, LH, PRL, and ACTH) in the same incubation medium showed that IL-1 beta did not alter their release. When the effects of IL-1 beta (1 pM-1 nM) and TNF alpha (100 pM) on TRH-induced TSH release were measured in short term experiments, the inhibitory effects had disappeared. The addition of 1-100 nM octreotide, a somatostatin analog, resulted in a decrease in TRH-induced TSH release up to 33% of the control value (P < 0.05). Exposure to dexamethasone (1 nM to 1 microM) affected basal and TRH-induced TSH release similar to the effect of IL-1 beta. The 15-min uptake of [125I]T3 and [125I]T4, expressed as femtomoles per pM free hormone, was not affected by the presence of IL-1 beta (1-100 pM). When IL-1 beta (100 pM) was present during 3 days of culture, TSH release was reduced to 88 +/- 2% of the control value (P < 0.05). This effect was not associated with an altered [125I]T3 uptake (15 min to 4 h) or with any change in nuclear T3 binding. We conclude that 1) IL-1 beta decreases TSH release by a direct action on the pituitary; 2) this effect is not due to elevated thyroid hormone uptake or increase T3 nuclear occupancy; 3) IL-1 beta does not affect TRH-induced TSH release or the release of other anterior pituitary hormones; and 4) TNF alpha affects basal and TRH-induced TSH release in the same way as IL-1 beta.

Animals↗
PubMed1996

Uptake and metabolism of 3,5,3'-triiodothyronine and 3,3',5'-triiodothyronine by human liver-derived cells: HepG2 cells as a model for thyroid hormone handling by human liver.

The uptake and metabolism of T3 and rT3 was studied in human liver-derived HepG2 cells. The results showed a saturable, time-dependent, and ouabain-sensitive increase in nuclear bound T3. The effects of ouabain (0.5 mmol/L) and unlabeled T3 (10 nmol/L and 10 mumol/L) were much more pronounced at the nuclear level, suggesting the presence of a nonspecific component in total cellular binding. Nuclear binding of rT3 remained below the detection limit in all experiments. Comparison of rT3 metabolism in HepG2 cells and primary cultures of rat hepatocytes showed an approximately 10-fold lower iodide production in HepG2 cells. Iodide production was decreased in the presence of ouabain and almost absent in the presence of propylthiouracil (100 mumol/L). Our data confirmed the presence of a carrier-mediated uptake system for both T3 and rT3. Metabolism data indicated functional type I deiodinase activity in HepG2 cells, the presence of glucuronidating enzymes, and the absence of thyroid hormone sulfotransferase activity. Based on these data, we propose that HepG2 cells provide an appropriate model for thyroid hormone handling by human liver. In addition, we suggest that in human liver sulfation of thyroid hormone, and therefore deiodination of T3 is of only minor importance.

Animals↗
PubMed1995

[Multiple pulmonary embolisms in nursing home patients recognizable by alertness to certain aspecific symptoms].

OBJECTIVE: To determine whether increased alertness regarding multiple pulmonary embolism in geriatric patients increases the number of cases diagnosed. DESIGN: Retrospective descriptive study. SETTING: Dutch nursing homes Mariënhaven (psychogeriatric) in Warmond and De Wilbert (somatic and psychogeriatric) in Katwijk aan den Rijn, the Netherlands. METHOD: In the period 1989-1991, the diagnosis of multiple pulmonary embolism was suspected in 15 patients with an 'unclear' or 'aspecific' complex of symptoms, who subsequently underwent ventilation perfusion scintigraphy. RESULTS: In 11/15 patients the diagnosis of multiple pulmonary embolism was confirmed. These patients were treated with anticoagulants resulting in complete recovery in 9 patients. Aspecific symptoms suggestive of pulmonary embolism include subfebrile temperature, respiratory and sensory disturbances and a clinical picture mimicking airway infection. If lung scintigraphy is only performed if a positive diagnosis will have the therapeutical consequences for the patients concerned, and assuming that refraining from treatment would lead to death, it was calculated that on a yearly basis mortality in subjects in nursing homes could be reduced by more than 2% when appropriate diagnosis is made and treatment given. Comparison of the data from SIG Health Information (Utrecht) with the present results suggests that the prevalence of (multiple) pulmonary embolism in the Dutch nursing homes is insufficiently recognized. CONCLUSION: More alertness regarding multiple pulmonary embolism in nursing home patients will establish the diagnosis more frequently and proper treatment of this condition will lead to a decrease in mortality.

Aged↗
PubMed1995

Pulmonary infarction caused by giant-cell arteritis of the pulmonary artery.

A 79-year-old woman presented with a pulmonary infarction concurrent with a relapse of giant-cell arteritis during tapering off of prednisone. As no origin for thromboembolism could be found, it is very probable that the thrombosis of the branch of the pulmonary artery was superimposed on local giant-cell vasculitis. Rapid clinical and laboratory recovery was achieved with anticoagulant therapy and by increasing the prednisone dosage. The literature on this rare manifestation of giant-cell arteritis is reviewed.

Aged↗
PubMed1995

Effects of a furan fatty acid and indoxyl sulfate on thyroid hormone uptake in cultured anterior pituitary cells.

A furan fatty acid, 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) and indoxyl sulfate (Indox) accumulate in serum of uremic patients and inhibit the active uptake of thyroxine (T4) into hepatocytes. We tested the effects of CMPF and Indox on the uptake of [125I]triiodothyronine (T3) and [125I]T4 and thyroid-stimulating hormone (TSH) release in anterior pituitary cells. Pituitary cells (500,000/well) were cultured for 3 days in medium with 10% fetal calf serum. Experiments were performed at 37 degrees C in the same medium with 0.5% bovine serum albumin (BSA; [125I]T3 uptake and TSH secretion) or 0.1% BSA ([125I]T4 uptake). The 15-min uptake of [125I]T3 amounted to 0.074 +/- 0.003 fmol/pM free T3 (n = 23) and that of [125I]T4 to 0.033 +/- 0.002 fmol/pM free T4 (n = 32). Preincubation (30 min) and incubation (15 min) with CMPF (20-200 microM) did not alter the uptake of [125I]T3 but reduced [125I]T4 uptake by 27% (P < 0.05) at the highest concentration tested. Indox (40-400 microM) did not affect the uptake of [125I]T3 or [125I]T4. CMPF (40 microM) and Indox (80 microM) did not directly affect the basal or thyrotropin-releasing hormone (TRH)-induced TSH release nor interfere with the effect of 10 nM T3 on TRH-induced TSH release. In conclusion, the absence of inhibitory effects of CMPF or Indox on thyroid hormone uptake by pituitary cells suggests that the transport mechanism is regulated differently compared with that in hepatocytes and underscores the significance of the thyroid hormone carriers for the intracellular availability of T3.

Animals↗
PubMed1995

Uptake of 3,3',5,5'-tetraiodothyroacetic acid and 3,3',5'-triiodothyronine in cultured rat anterior pituitary cells and their effects on thyrotropin secretion.

We compared the uptake, metabolism, and biological effects of tetraiodothyroacetic acid (Tetrac) and rT3 in anterior pituitary cells with those of T4 and T3. Cells were isolated from adult male Wistar rats and cultured for 3 days in medium with 10% fetal calf serum. Uptake was measured at 37 C in medium with 0.1% BSA for [125I]Tetrac (200,000 cpm; 240 pM) and [125I]T4 (100,000 cpm; 175 pM) or with 0.5% BSA for [125I]rT3 (100,000 cpm; 250 pM) and [125I]T3 (50,000 cpm; 50 pM). The free fraction of Tetrac was 1% that of T4 (in medium with 0.1 and with 0.5% BSA), and the free fraction of rT3 was half that of T3. Uptake of the four tracers increased sharply up to 1 h of incubation and then leveled off. Expressed as femtomoles per pM free hormone, uptake at equilibrium was 1.16 +/- 0.16 (n = 6) for Tetrac, 0.15 +/- 0.01 (n = 6) for T4, 0.023 +/- 0.003 (n = 6) for rT3, and 0.21 +/- 0.02 (n = 6) for T3. Cell-associated radioactivity after incubation for 24 h with [125I]Tetrac was represented for 15% by [125I]Triac; after incubation with [125I]T4 for 15-20% by [125I]T3, after incubation with [125I]rT3 for 6% by [125I]3,3'-T2, while [125I]T3 was still for 98% [125I]T3. Exposure of cells for 2 h to 100 nM TRH stimulated TSH release by 90-135%. Tetrac was effective in reducing this response at a free concentration of 0.05 pM, but rT3 was effective only at a free concentration of 16 nM. A free Tetrac concentration of 5 pM was equally effective as 50 pM free T4 in reducing the TSH response to TRH. In human serum, Tetrac was exclusively bound to T4-binding prealbumin. The free Tetrac fraction was 0.001% in control subjects and rose 2- to 12-fold in patients with nonthyroidal illness. As uptake of [125I]Tetrac in the pituitary was higher than that of T4 and T3, and it was more potent than T4 in reducing TSH release, Tetrac may be of potential significance for the regulation of TSH secretion in vivo.

Animals↗
PubMed1995

Impaired thyroxine and 3,5,3'-triiodothyronine handling by rat hepatocytes in the presence of serum of patients with nonthyroidal illness.

In systemic nonthyroidal illness (NTI), peripheral production of T3 from T4 is decreased, resulting in a decreased serum T3 concentration. We investigated whether factors in serum of NTI patients may play a role in this energy-saving adaptation mechanism. Metabolism of T4 and T3 by rat hepatocytes in primary culture was measured in the presence of 10% serum of normal subjects or of patients with NTI and related to the severity of disease. Patients with NTI were grouped according to serum thyroid hormone abnormalities: group I, serum rT3, T3, and T4 normal; group III, rT3 elevated, T3 decreased, T4 normal; group IV, rT3 elevated, T3 and T4 decreased. Compared with metabolism in the presence of normal serum, metabolism of T4 and to a lesser extent of T3 was progressively decreased in the presence of serum of patients of groups I-IV. A decreased net deiodination of T4 and T3 (corrected for differences in free hormone concentration) without an increase in conjugated T4 and T3 (corrected for differences in free hormone concentration) was observed, similar to results in experiments with compounds inhibiting transport into the cells and not the metabolic processes (5' deiodination) per se. Deiodination of T4 in vitro was correlated with serum T3 concentration of the patient (r = 0.69). Serum of patients with NTI influences thyroid hormone handling by hepatocytes comparable to the effect of transport inhibitors and not to that of the 5'-deiodinase inhibitor propylthiouracil, suggesting that decreased thyroid hormone transport over the cell membrane may play a role in lowered T3 production in NTI.

Animals↗
PubMed1994

Adaptive changes in transmembrane transport and metabolism of triiodothyronine in perfused livers of fed and fasted hypothyroid and hyperthyroid rats.

The transport and subsequent metabolism of triiodothyronine (T3) were studied in isolated perfused livers of euthyroid, hypothyroid, and hyperthyroid rats, both fed and 48-hour-fasted. T3 kinetics (transport and metabolism) during perfusion were evaluated by a two-pool model, whereas the metabolism of T3 was also investigated by determination of T3 breakdown products by chromatography of medium and bile. For comparison of groups, metabolism was corrected for differences in transport. Transport parameters in fed hypothyroid livers were not significantly changed as compared with euthyroid livers, whereas metabolism was decreased. In fed hyperthyroid livers, fractional transfer rate constants for influx (k21) and efflux (k12) were decreased and metabolism, corrected for differences in intracellular mass transfer, was increased. Furthermore, for transport in hyperthyroid liver it was shown that only total mass transfer (TMT) into the metabolizing liver compartment (not into the nonmetabolizing liver compartment) was decreased. Transport and metabolic parameters in fasted hypothyroid livers were decreased as compared with euthyroid fed livers. In fasted hyperthyroid livers, transport and metabolism were not significantly different as compared with that in euthyroid fed livers, so transport was increased versus hyperthyroid fed livers. It appeared therefore that fasting normalized the effects of hyperthyroidism on both the transport and metabolic processes of T3 in the liver. The present study demonstrates normal transport and decreased metabolism in livers of hypothyroid fed rats and decreased transport and increased metabolism in livers of hyperthyroid fed rats. In livers of hypothyroid fasted rats transport and metabolism were decreased, whereas in livers of hyperthyroid fasted rats transport and metabolism were not significantly different from that in euthyroid fed livers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological↗
PubMed1994

Uptake of triiodothyronine sulfate and suppression of thyrotropin secretion in cultured anterior pituitary cells.

To investigate the uptake of triiodothyronine sulfate (T3S) and its effect on thyrotropin-releasing hormone (TRH)-induced thyrotropin (TSH) secretion, anterior pituitary cells were isolated from euthyroid rats and cultured for 3 days in medium containing 10% fetal calf serum. Incubation was performed at 37 degrees C in medium containing 0.5% bovine serum albumin (BSA). Exposure of the pituitary cells to TRH (0.1 mumol/L) for 2 hours stimulated TSH secretion by 176%. This effect was reduced by approximately 45% after a 2-hour preincubation with T3 (0.001 to 1 mumol/L). A significant inhibitory effect of T3S on TRH-induced TSH release was only observed at a concentration of 1 mumol/L. The uptake of [125I]T3 after 1 hour of incubation was reduced by 40% +/- 4% (P < .001) by simultaneous addition of 10 nmol/L unlabeled T3, whereas 1 mumol/L T3S was required to obtain a reduction of the [125I]T3 uptake by 34% +/- 2% (P < .001). The amount of T3 present in the unlabeled T3S preparation was 0.25% as determined by radioimmunoassay. When pituitary cells were incubated for 1 hour with [125I]T3S or [125I]T3 (both 50,000 cpm/0.25 mL), the uptake of [125I]T3S expressed as a percentage of the dose was 0.04% +/- 0.02% (mean +/- SE, n = 4), whereas that of [125I]T3 amounted to 3.0% +/- 0.4% (n = 4). In contrast, when hepatocytes were incubated for 1 hour with [125I]T3S, the uptake amounted to 5.1% +/- 0.8% (n = 9), whereas that of [125I]T3 was 22.1% +/- 1.7% (n = 9).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Transport of thyroxine into cultured hepatocytes: effects of mild non-thyroidal illness and calorie restriction in obese subjects.

OBJECTIVE: Inhibitors of cellular T4 transport leading to diminished plasma T3 production have been identified as 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid (CMPF) and indoxyl sulphate in uraemia and bilirubin and non-esterified fatty acids (NEFA) in critically ill patients with hyperbilirubinaemia. We question whether other factors are responsible for the altered thyroid hormone parameters observed in mild illness and during calorie restriction. PATIENTS: We studied (i) 18 non-uraemic patients with non-thyroidal illness (NTI) (T4 > or = 60, T3 < or = 1.1 and rT3 > or = 0.45 nmol/l) with serum molar ratios of bilirubin:albumin < or = 0.17 and NEFA:albumin < or = 2.6. These molar ratios have been shown to be the minimum ratios which inhibited T4 transport into rat hepatocytes; (ii) four obese euthyroid subjects on 600 kcal/day for 10-14 days. This diet is known to inhibit the unidirectional T4 transport into human liver in vivo. MEASUREMENTS: We measured iodide production from 125I-T4 by incubating rat hepatocytes with 10% human serum. The deiodination of T4 was used as an index of cellular transport of T4 in vivo. RESULTS: The mean iodide production from 125I-T4 by rat hepatocytes in the presence of 10% serum from NTI patients (98 +/- 17%, mean +/- SD) was not significantly different from the normals (100 +/- 9%). Calorie restriction in euthyroid obese subjects resulted in a small but significant reduction (-12%) of iodide production. Calorie restriction increased the total serum NEFA by 91%. CONCLUSIONS: Our study demonstrates that CMPF, indoxyl sulphate, bilirubin and NEFA are not responsible for the inhibition of T4 tissue uptake in patients with mild illness. In addition, studies with calorie restricted obese subjects indicate that high concentration of NEFA during calorie restriction inhibits T4 tissue uptake. This inhibition may partly explain the lower plasma T3 during calorie restriction.

Bilirubin↗
PubMed1994

Different effects of amiodarone on transport of T4 and T3 into the perfused rat liver.

Uptake and metabolism of thyroxine (T4) and 3,5,3'-triiodothyronine (T3) were studied in isolated perfused livers of control and amiodarone-treated rats (40 mg.kg body wt-1.day-1, 22 days). With the use of this perfusion system and a two-pool model describing thyroid hormone kinetics, total uptake was evaluated by the half-time (t1/2) of the fast component of the biphasic thyroid hormone disappearance from the medium and by the fractional influx rate constant (k21). Metabolism was assessed by the t1/2 of the slow component, by determination of breakdown products in medium and bile, and by thyroid hormone disposal according to the two-pool model. Disposal was corrected for differences in mass transfer into the metabolizing pool. In amiodarone-treated rats, both uptake and metabolism of T4 were decreased. Furthermore, it was shown that only transport into the metabolizing liver compartment and not uptake into the nonmetabolizing liver compartment was decreased. Both uptake and total metabolism of T3 were unaffected by amiodarone. The results showed that the different transport systems for T4 and T3 described in isolated rat hepatocytes may also be operative in the intact rat liver. Furthermore, it can be concluded that the low-T3 syndrome, caused by treatment with amiodarone, may be due to both impaired transport and impaired 5'-deiodination.

Amiodarone↗
PubMed1994

T4 uptake into the perfused rat liver and liver T4 uptake in humans are inhibited by fructose.

Recently, we described a two-pool model for 3,5,3'-triiodothyronine uptake and metabolism in the isolated perfused rat liver. Here, we applied this model to investigate transmembrane thyroxine (T4) transport and its possible ATP dependence in vivo. These studies are performed in perfused rat livers during perfusion with or without fructose in the medium, as it has been shown that intracellular ATP is decreased after fructose loading. Furthermore, we studied serum T4 tracer disappearance curves in four human subjects before and after intravenous fructose loading. In the perfused rat liver, we found a decrease in liver ATP concentration and a decrease in medium T4 disappearance and T4 uptake in the liver pool after fructose. Furthermore, it was shown that, when corrected for differences in the medium free hormone concentration, only transport to the metabolizing liver pool was decreased after fructose perfusion, whereas uptake in the nonmetabolizing pool was unaffected. Disposal, corrected for differences in transport into the metabolizing pool, was also not affected after fructose. In the human studies, intravenous fructose administration induced a rise in serum lactic acid and uric acid, indicating a decrease in liver ATP. This was observed concomitant with a decrease in serum tracer T4 disappearance during the first 3 h after fructose administration. These results suggest ATP dependence of transport of iodothyronines into the liver in vivo and show that, in the rat liver and in humans, uptake of T4 may be regulated by intracellular energy stores; in this way the tissue uptake process may affect intracellular metabolism and bioavailability of thyroid hormone.

Adenosine Triphosphate↗
PubMed1994

Uptake of thyroxine in cultured anterior pituitary cells of euthyroid rats.

The uptake of [125I]T4 was investigated in cultured anterior pituitary cells isolated from adult fed Wistar rats and cultured for 3 days in medium containing 10% fetal calf serum. Experiments were performed with [125I]T4 (10(5) to 2 x 10(6) cpm; 0.35-7 nM) in medium containing 0.5% or 0.1% BSA. The uptake of [125I]T4 increased with time and showed equilibrium after around 1 h of incubation. The presence of 10 microM unlabeled T4 during incubation decreased the uptake of [125I]T4 by 65-70% at all time intervals. After 24 h of incubation, 1.5% iodide and 3.2% conjugates were detected in the medium, whereas around 20% of cellular radioactivity represented [125I]T3. The 15-min uptake of [125I]T4 was significantly reduced by simultaneous incubation with 100 nM T4 (by 24%; P < 0.05), 100 nM T3 (by 38%; P < 0.001), or 10 microM rT3 (by 32%; P < 0.001), whereas 10 microM tetraiodothyroacetic acid (Tetrac) had no effect. Furthermore, preincubation (30 min) and incubation (15 min) with 10 microM monodansylcadaverine, oligomycin, or monensin reduced the uptake of [125I]T4 by 30%, 50%, and 40%, respectively (all P < 0.001). Substitution of Na+ in the buffer by K+ diminished the uptake of [125I]T4 by 39% (P < 0.005); 2 mM phenylalanine, tyrosine, or tryptophan reduced [125I]T4 uptake by 18% (P < 0.05), 18% (P = NS), and 33% (P < 0.005), respectively. Our data suggest that the pituitary contains a specific carrier-mediated energy-requiring mechanism for [125I]T4 uptake that is partly dependent on the Na+ gradient. In addition, part of [125I]T4 uptake in the pituitary might occur through an amino acid transport system. When expressed per pM of free hormone, the 15-min uptake of [125I]T4 was approximately as high as that of [125I]T3. Because the reduction of [125I]T4 uptake by T4, T3, monodansylcadaverine, oligomycin, and monensin was roughly the same as the previously reported reduction of [125I]T3 uptake by the same compounds, it is further suggested that T4 and T3 share a common carrier in cultured anterior pituitary cells.

Animals↗
PubMed1994

Uptake of triiodothyroacetic acid and its effect on thyrotropin secretion in cultured anterior pituitary cells.

The uptake of [125I]triiodothyroacetic acid ([125I]Triac) in anterior pituitary cells was investigated and compared with that of [125I]T3. Furthermore, the effects of Triac, T3, and T4 on TSH release were compared. Cells isolated from adult male Wistar rats were cultured for 3 days in medium with 10% fetal calf serum. Uptake was measured at 37 C with [125I]Triac (100,000 cpm; 120 pM) or [125I]T3 (50,000 cpm; 50 pM) in medium with 0.5% BSA. In this medium, the ratio of the free fractions of Triac, T3, and T4 was 1:8:1. Exposure of cells to 100 nM TRH for 2 h stimulated TSH release by 80-110% (P < 0.001). Comparing total hormone levels (1 nM to 1 microM), Triac and T3 were equally effective in reducing this response, and both were 10-fold more effective than T4. The time course (15 min to 4 h) of [125I]Triac uptake was similar to that of [125I]T3, showing equilibrium after 1 h. Unlabeled Triac (1 microM) reduced the uptake of [125I]Triac and [125I]T3 at all time intervals. Expressed per pM free hormone, the cellular and nuclear uptake of [125I]Triac were twice those of [125I]T3. The 15-min uptake of [125I]Triac was reduced by incubation with 10 nM unlabeled Triac (35%; P < 0.001). Maximum inhibition (56%; P < 0.001) was found with 10 microM Triac. A similar effect was seen with 10 microM T3, T4, or 3,3',5,5'-tetraiodothyroacetic acid. Preincubation (30 min) and incubation (15 min) with 10 microM oligomycin reduced the cellular ATP content by 51% (P < 0.001), [125I]T3 uptake by 77% (P < 0.001), and [125I]Triac uptake by only 25% (P < 0.001). The temperature dependence of [125I]Triac and [125I]T3 uptake was the same. Preincubation and incubation with 10 microM monensin (reduces the Na+ gradient) or 10 microM monodansylcadaverine (inhibits receptor-mediated endocytosis) reduced 15-min [125I] Triac uptake by 15% (P < 0.005) and 19% (P < 0.005), respectively. The data show that 1) Triac, on the basis of the free hormone concentration, is more potent than T3 or T4 in suppressing TSH secretion; and 2) the rapid uptake of [125I]Triac by the anterior pituitary occurs by a carrier-mediated mechanism that is only partially dependent on ATP or the Na+ gradient.

Animals↗
PubMed1993

Reduced T3 deiodination by the human hepatoblastoma cell line HepG2 caused by deficient T3 sulfation.

Type I deiodination of T3 sulfate occurs at a Vmax that is 30-fold higher as compared to T3, both in rat and in human liver homogenates. We now present data showing lack of T3 deiodination by a human liver derived hepatoblastoma cell line, HepG2, caused by deficient T3 sulfation. Cellular entry of T3 was assessed by its nuclear binding after whole cell incubation. In spite of the presence of type I deiodinase, as confirmed by T4 and rT3 deiodination in homogenates, no deiodination of T3 could be detected. Since HepG2 cell homogenates also deiodinated chemically synthesized T3 sulfate (T3S) and inhibition of type I deiodination by propylthiouracil (PTU) did not cause T3S accumulation in whole cell incubations, we conclude that (i) HepG2 cells show reduced T3 deiodination caused by deficient T3 sulfation, and (ii) sulfation of T3 is an obligatory step prior to hepatic deiodination.

Animals↗
PubMed1993

The importance of thyroid microsomal antibodies in the development of elevated serum TSH in middle-aged women: associations with serum lipids.

OBJECTIVE: We assessed the relative risk of both serum TSH and antithyroid antibody concentrations with regard to progression of thyroid failure and studied the lipid profiles of individuals with elevated TSH levels. DESIGN, PATIENTS AND MEASUREMENTS: In a randomly selected group of 427 women aged 40-60 (mean 55) years volunteering in an epidemiological survey in Zoetermeer, TSH and thyroid microsomal antibodies (TMA) were determined. Ten years after the initial survey only TSH was measured and the lipid profiles of the individuals with elevated serum TSH levels were studied and compared with a reference group. RESULTS: During follow-up, four of 427 women were treated with thyroxine. Seventeen of 423 women initially had elevated serum concentrations of TSH (> 4.2 mU/l), 11 of whom were TMA positive. In the group of 406 women with initially a normal TSH, nine out of 37 (24%) TMA-positive women developed elevated serum levels of TSH over 10 years. In contrast only 10 of 369 (3%) TMA-negative women had elevated serum TSH levels 10 years after the initial survey (P < 0.001). Altogether, at the end of the observation period, 40% of TMA-positive subjects had elevated serum TSH concentrations, compared to 3% in the TMA-negative group (P < 0.01). TSH levels in the upper part of the normal range also appeared to have a predictive value: if those both with TSH levels between 2.0 and 4.2 and with a positive TMA status were contrasted with those without antibodies and low TSH, the crude relative risk was 71.5 (31.0-164.3), whereas the crude relative risk of presence versus absence of TMA was only 36.3 (18.8-70.3). Women with elevated TSH levels did not show changes in serum concentrations of total cholesterol (7.4 +/- 1.1 mmol/l), apo-A, (4.7 +/- 1.0 mmol/l) and apo-B (3.1 +/- 0.7 mmol/l) lipoproteins, compared with control individuals (7.2 +/- 1.3, 4.7 +/- 0.8 and 3.0 +/- 0.7 mmol/l, respectively). CONCLUSIONS: The determination of serum TMA in middle-aged women can identify an important group of women at risk of developing an elevated serum TSH. TMA measurement is of potential use in the prevention of cardiovascular disease. An elevated serum TSH, however, in our study-group does not seem to be accompanied by an abnormal lipid profile, as reported by others.

Adult↗