共查询到20条相似文献,搜索用时 15 毫秒
1.
T. Valcana 《Neurochemical research》1981,6(7):743-753
In this study we have examined whether rat brain nuclear thyroid hormone receptors bind T4 or metabolites of T4 and whether there is a developmental change in brain T4 metabolism and binding. Developing animals were injected with trace [125I]3,5-tetraiodothyronine ([125I]T4) and after sacrifice brain nuclear and cytoplasmic fractions were examined to determine whether their radioactivity was represented by the injected [125I]T4 or any of its metabolites. Of the radiothyronines specifically bound to the nucleus, 90% was found to be triiodothyronine ([125I] T3) and 10% was [125I]T4. Of the cytoplasmic, protamine sulfate-precipitable fraction, 40% was [125I]T4 and 60% [125I]T3. Inasmuch as the percentage of [125I] T3 found in plasma during the same postinjection interval was similar to that present as contaminant of the injected material, it was concluded that brain [125I] T3 derives from local monodeiodination of T4 to T3. The main developmental change observed was a marked decline in the total cytoplasmic and nuclear [125I] T4 uptake. However, with development, the T3/T4 ratio remained constant in the nuclear fraction while it decreased in the cytoplasmic fraction. It is concluded that although T3, deriving from monodeiodianation of T4, is the main form of thyroid hormone that regulates brain development by its binding to brain nuclear receptors, the fact that T4 is the most available from during the critical period makes it, indirectly, very important to brain development. Further, the decline observed with development in T4 uptake and monodeiodination to T3, may contribute to the concomitantly declining role of thyroid hormones on brain tissue. 相似文献
2.
Selenoenzyme activities in selenium- and iodine-deficient sheep 总被引:3,自引:0,他引:3
Voudouri AE Chadio SE Menegatos JG Zervas GP Nicol F Arthur JR 《Biological trace element research》2003,94(3):213-224
This study was conducted to evaluate the effects of single and combined deficiencies of selenium and iodine on selenoenzyme
activities in sheep. Twenty-four male lambs were assigned to one of four semisynthetic diets: combined deficient A (Se−I), Se-deficient B (Se−I+), I-deficient C (Se+I−), and basal diet D (Se+I+). Thyroid hormones (T3, T4), thyroid stimulating hormone (TSH), and inorganic iodine (PII) were determined in plasma. Selenium and glutathione peroxidase
activity (GSH-Px) were determined in erythrocytes, and tissue samples, including the thyroid, liver, kidney, and brain, were
taken for selenoenzyme analysis. Plasma T3, T4, and TSH concentrations were similar in all groups. Type I deiodinase (ID-I) activity in liver and kidney remained unchanged
in Se or I deficiency. In contrast, hepatic ID-I activity was increased by 70% in combined Se-I deficiency. Thyroidal cystolic
GSH-Px (c-GSH-Px) and phospholipid GSH-Px (ph-GSH-Px) activities remained constant in both Se-deficient groups, whereas thyroidal
c-GSH-Px activity increased (57%) in I deficiency. Type II deiodinase (ID-II) activity was not detectable in the cerebrum
and cerebellum, whereas cerebellum Type III deiodinase (ID-III) activity was decreased in I deficiency and combined Se-I deficiencies.
The results of the present study support a sensitive interaction between Se and I deficiencies in sheep thyroid and brain.
Furthermore, the lack of thyroidal ID-I activity, the presservation of the thyroidal antioxidant enzymes, and the increases
in hepatic ID-I indicate that a compensatory mechanism(s) works toward retaining plasma T3 levels, mostly by de novo synthesis of T3 and peripheral deiodination of T4 in Se- and I-deficient sheep. 相似文献
3.
Kenji Sorimachi Akira Niwa Yasumura Yosihiro 《Biochimica et Biophysica Acta (BBA)/General Subjects》1980,630(4)
The cultured rat hepatoma cell (R117-21B) homogenates metabolized 3,[3′,5′-125I]triiodothyronine by phenolic ring deiodination and produced radioactive iodide and 3,3′-diiodothyronine. Thyroxine (T4) was converted to 3,3′,5-triidothyronine (T3). The production of 125I− presented the deiodinase activity. The optimal pH for phenolic ring deiodination was observed to be pH 6.0–7.0. This enzyme reaction was accelerated by dithiothreitol. Propylthiouracil strongly inhibited the phenolic ring deiodination at 0.1 mM, whereas an effect of 20 mM methylmercaptoimidazol on the deiodination was very weak or absent.Excess unlabeled iodothyronines (T4, T3 and 3,5-diiodo-l-thyronine inhibited the phenolic ring deiodination of labeled 3,3′,5′-triiodothyronine, althought their inhibitory effect was slightly different. Triiodothyroacetic acid was a better inhibitor than T3. Diiodotyrosine did not affect phenolic ring deiodination in cultured rat hepatoma cell homogenates.Phenolic and nonphenolic ring deiodinase activities of cultured monkey hepatocarcinoma cell and rat liver homogenates were also studied by the use of 3,[3′,5′-125I]triiodothyronine and [3,5-125I]thyroxine, respectively. Both deiodinase activities were observed in particulate fractions (mitochondrial and microsomal) of cultured cell and rat liver homogenates. 相似文献
4.
Measurement and regulation of thyroidal status in teleost fish 总被引:5,自引:0,他引:5
Summary We have reviewed the stages in teleost thyroid function and its regulation, from the initial biosynthesis of the TH to their eventual interaction with putative receptors.TH biosynthesis depends on an adequate plasma iodide level, determined partly by dietary iodide and partly by active branchial iodide uptake from the water, Pulse-injected radioiodide can be used to evaluate thyroidal iodide uptake, aspects of TH biosynthesis and TH thyroidal secretion. However, owing to variable plasma iodide levels, care is required in interpretating these parameters. TH biosynthesis, thyroglobulin properties and intrathyroidal secretion mechanisms have received limited recent attention. Histological indices of thyroid tissue changes, while useful in many situations, do not always correlate with more direct estimates of thyroidal secretion and can be misleading.Thyroid function is regulated by the hypothalamo-pituitary-thyroid axis, but neither the identities of the hypothalamic factors nor a reliable immunoassay for TSH have been established. Currently, activity of the hypothalamic-pituitary axis is usually determined by pituitary thyrotrope histological appearance or bioassay of pituitary TSH. Plasma free T4 feeds back at both the pituitary and hypothalamic levels and inhibits TSH release. Thyroidal T4 secretory activity is presumably adjusted to maintain a constant plasma T4level according to physiologic state.Plasma T4 is probably the most commonly used index of thyroidal status. However, (1) T4 is probably not the active form of TH, (2) the T4 plasma level may be influenced by the binding properties of plasma proteins, and (3) the T4 concentration alone makes no provision for the rate of T4 turnover in plasma. The most practical way to measure thyroidal T4SR is to determine plasma T4DR, and assuming steady-state conditions, equate it to T4SR. The T4DR is determined from kinetic studies employing*T4, which also enable estimates of sizes of vascular and extravascular T4 pools and their rates of exchange. Excretion of T4 or its derivatives in urine or bile can be determined also. A high proportion of T4 is enzymatically monodeiodinated in liver and other tissues, generating T3 for local (intracellular) and vascular systemic compartments.Bothin vivo andin vitro methods have been used to quantify T4 deiodinase activity, which is highly responsive to physiologic state and environmental variables. T3 production is inhibited by a moderate T3 excess indicating an autoregulatory system, whereby tissue T3 levels are maintained at a set-point appropriate for a particular physiologic state. The rate of T3 production provides an informative measure of thyroidal status in a given tissue. However, other pathways also contribute to the maintenance of T3 homeostasis at a particular set-point. These include the rate of T3 degradation to 3,3-T2, the rate of T4 substrate diversion to rT3 (an inactive isomer) and by the excretion of parent compounds or conjugates in bile and urine. Potential losses across branchial or integumentary surfaces have yet to be evaluated.The most fundamental measure of thyroidal status is represented by the amount of T3 saturably bound to receptors/nucleus for the cell type of interest. This is estimated most accurately in double isotope studies in which T3 contributions from both vascular and intracellular compartments are evaluated. Less satisfactory but meaningful indices of T3 availability to receptor sites may be obtained from the plasma T3 (or free T3) level and from the tissue T3 level. The former is appropriate if the cell type in question obtains its T3 primarily from plasma; the latter should be measured if the cell type derives its T3 mainly through intracellular deiodinase activity. If the proportion of vascular T3/intracellular T3 bound to receptors is known, it may indicate the degree of receptor activation. However, even cytosolic T3 levels may not vary in proportion to nuclear T3 levels.Differences in thyroidal function between teleosts and homeotherms can be attributed to distinctive strategies in iodide economy and to fundamental differences in control of thyroidal status. Owing to more certain iodide availability (branchial iodide pump and plasma iodide-binding proteins), teleosts are probably more liberal in their iodide use and have less efficient mechanisms for recovery and retention of hormonal iodide than homeotherms. Also, primary control of teleost thyroidal function appears peripheral. It is the finely regulated conversion of T4 to T3 in tissues which may largely determine the T4 secretion rate. Thus, T4, as a prohormone, may be produced more to satisfy the substrate needs for T4 conversion rather than to drive T3 production. Because TH are mainly implicated in tissue- or cell-specific processes involved in development, growth and reproduction in teleosts, it may be advantageous for their thyroidal status to be determined locally through T4-to-T3 deiodination. In homeotherms, primary control is mainly central through the hypothalamic-pituitary axis, which regulates thyroidal secretion of T4 and significant amounts of T3. The level of T4 (free T4) is believed to drive the production of T3 in most peripheral tissues. Because TH are extensively involved in the systemically integrated adjustment of basal metabolic rate in homeotherms, it may have been advantageous to evolve a system leaning towards central control by the hypothalamus, the brain centre associated with thermoregulation. 相似文献
5.
《Biochemical medicine》1983,29(1):85-95
Gel filtration of dog myocardial cytosol previously incubated with [125I]T4 or [125I]T3 revealed hormone binding in three fractions, one of which, M-2, was presumptively identified as myoglobin by absorbance maximum, molecular weight and specific immunodiffusion. Gel chromatography of purified horse or dog myoglobins incubated with labeled T3 or T4 resulted in coelution of the myglobin and iodothyronine peaks. Excess unlabeled thyroid hormone displaced no more than 25% of tracer bound to myoglobin. Acid-acetone fractionation of myoglobin into heme and globin, and subsequent precipitation of the heme, localized hormone binding to the heme moiety. Hematin (ferric state heme) in solution was also shown to bind thyroid hormone.Added to human sera which were then subjected to T3 or T4 radioimmunoassay, myoglobin reduced detectable, endogenous iodothyronine by 77 and 26%, respectively. The myoglobin effect was concentration dependent.Heart myoglobin, like hemoglobin in the erythrocyte, is a cytoplasmic heme protein responsible for a major fraction of binding of intracellular iodothyronine. The nature of the interaction between iodothyronines and the heme prosthetic group is unclear. 相似文献
6.
Many steroid and thyroid hormones and some drugs are bound by circulating red cells. Red cell-bound ligand may not be physiologically inert, as recent studies show that red cell-bound drug is available for uptake by brain. To investigate whether triiodothyronine (T3) is available for uptake by brain in vivo from the circulating red cell pool, the present investigations measure the effects of human erythrocytes on rat brain uptake of [125I]T3 in vivo. The fraction of circulating T3 available for uptake in vivo in the presence of 0, 2, 5, 10, 22, or 44% red cells was essentially identical to the fraction of [125I]T3 unbound in vitro. Therefore, [125I]T3 bound to red cells obtained from normal volunteers is not available for uptake by brain in vivo. 相似文献
7.
A series of chaclone derivatives containing an indole moiety were evaluated in competitive binding assays with Aβ1-42 aggregates versus [125I]IMPY. The affinity of these compounds ranged from 4.46 to >1008 nM, depending on the substitution on the phenyl ring. Fluorescent staining in vitro showed that one compound with a N,N-dimethylamino group intensely stained Aβ plaques within brain sections of AD transgenic mice. The radioiodinated probe [125I]-(E)-3-(1H-indol-5-yl)-1-(4-iodophenyl)prop-2-en-1-one, [125I]4, was prepared and autoradiography in sections of brain tissue from an animal model of AD showed that it labeled Aβ plaques specifically. However, experiments with normal mice indicated that [125I]4 exhibited a low uptake into the brain in vivo (0.41% ID/g at 2 min). Additional chemical modifications of this indole-chalcone structure may lead to more useful imaging agents for detecting β-amyloid plaques in the brains of AD patients. 相似文献
8.
The radioiodinated pindolol analogs 125I-labeled cyanopindolol ([125I]CYP) and 125I-labeled hydroxybenzylpindolol ([125I]HBP) have been used to study binding to human platelet β-adrenergic receptors. [125I]CYP binds to a saturable class of binding sites on platelet membranes with a dissociation constant (Kd) of 14±3 pM and maximal binding capacity (Bmax) of 18±4 fmol/mg protein. Binding of [125I]CYP is reversible and is characterized by forward and reverse rate constants of 1.8·107 s?1·M?1 and 3.8·10?4 s?1, respectively. [125I]HBP binds to a saturable class of platelet membrane sites with a Kd of 50±10 pM and Bmax of 32±6 fmol/mg protein. [125I]HBP also binds to a saturable class of sites on intact platelets with a Kd of 58±14 pM and Bmax of 24±4 molecules per platelet. Binding of [125I]CYP and [125I]HBP is stereospecifically inhibited by propranolol and epinephrine; the (?) stereoisomers are at least 50-times more potent than the (+) stereoisomers. Binding of both radioligands is inhibited by adrenergic ligands with a potency order of propranolol ? isoproterenol > epinephrine > practolol > norepinephrine > phenylephrine. These observations indicate that [125I]CYP and [125I]HBP bind to platelet sites which have the pharmacological characteristics of β-adrenergic receptors but which are not typical of either the β1 or β2 sub-type. 相似文献
9.
Highly purified nuclei isolated from bovine corpora lutea showed marked enrichment of NAD pyrophosphorylase, a marker for this organelle. Rough endoplasmic reticulum and lysosomal markers were undetectable, whereas plasma membrane and Golgi markers were detectable but not enriched in nuclei. These highly purified nuclei exhibited specific binding with 125I-labeled human choriogonadotropin, [3H]prostaglandin E1 and [3H]prostaglandin F2α. However, these bindings were only 15.4% (human choriogonadotropin), 7.9% (prostaglandin E1) and 8.9% (prostaglandin F2α) of the plasma membrane binding observed under the same conditions. Washing of nuclei and plasma membranes twice with buffer containing 0.1% Triton X-100 resulted in gonadotropin and prostaglandin F2α binding site and 5′-nucleotidase (EC 3.1.3.5) losses from nuclei that were different from those observed for plasma membranes. More importantly, the washed nuclei exhibited 44% (human choriogonadotropin), 21–26% (prostaglandins) of original specific binding despite virtual disappearance of 5′-nucleotidase activity. The nuclear membranes isolated from nuclei, specifically bound 125I-labeled human choriogonadotropin and [3H]prostaglandin F2α to the same extent or significantly more ([3H]prostaglandin E1, P < 0.05) than nuclei themselves, despite the marked losses of chromatin. In summary, our data suggest that gonadotropin and prostaglandins bind to nuclei and that this binding was intrinsic and was primarily associated with the nuclear membrane. 相似文献
10.
《Journal of receptor and signal transduction research》2013,33(1-3):385-405
AbstractThe pharmacological profile and localization of somatostatin (SRIF) receptors were determined in rat, monkey and human cerebellum. In rat cerebellar cortex, low ss1/sst4, intermediate sst2 and very high sst3 receptor mRNA levels were found, sst1 mRNA was also expressed in the deep cerebellar nuclei. [125I]Tyr3-octreotide binding sites in cerebellar membranes correlated with recombinant sst2, but not with sst5 or sst3 receptors and were found in the molecular layer of the cerebellum. [125I]CGP 23996 (in Na+-buffer) binding in rat cerebellum correlated with sst1 or sst4, but not with sst2, sst3 or sst5 receptor binding. Similar data were obtained in rhesus monkey cerebellum. mRNAs for all five receptors were found in the granule cell layer of the human cerebellum and/or in the dentate nucleus. [125I]Tyr3-octreotide binding was strong in the molecular layer and correlated with that of recombinant sst2 receptors, but not with sst3 or sst5 receptors. [125I]CGP 23996 (in Mg++-buffer) binding was heterogeneous (about 75%. to sst2 and 25% to sst1 and/or sst4 receptors). The molecular and granular layers were equally and the dentate nucleus strongly labeled. Thus. SRIF receptors of the sst2, sst1 and/or sst4 subtype are present in the rat, monkey and human cerebellum. In the latter two species, the sst2 type appears to be predominant. Surprisingly, the high expression of sst3 receptor mRNA is not supported by radioligand binding data in any of the species studied. The reason for this discrepancy remains to be elucidated. 相似文献
11.
Kenji Sorimachi Jacob Robbins 《Biochimica et Biophysica Acta (BBA)/General Subjects》1979,583(4):443-453
Iodothyronine monodeiodinase activities in homogenates of cultured monkey hepatocarcinoma cells were measured by the deiodination of [3,5-125I]triido-l-thyronine or 3-[3′5′-125I]triido-l-thyronine (phenolic ring-labeled ‘reverse’ triiodothyronine). The assay system utilized a small ion-exchange column (AG50W-X4, 0.9×~1 cm) to measure 125I?. Both deiodinases were destroyed by boiling for 1 min.Maximal nonphenolic ring deiodination was observed at pH 7.9 whereas maximal phenolic ring deiodination was at pH 6.3. Both reactions were enhanced strongly by dithiothreitol (0.1–5 mM), and slightly by 5 mM β-mercaptoethanol. Phenolic ring deiodination was strongly inhibited by 0.1 mM propylthiouracil. Nonphenolic ring deiodination was accelerated by EDTA (1.2 mM) and inhibited by Mg2+ (5 mM). Methylmercaptoimidazol and Mg2+, Ca2+ and Mn2+ (0.1–1.0 mM) had little or no effect on either reaction, but Zn2+ (0.1 mM) strongly inhibited both.Both reactions were inhibited by excess iodothyronine analogues at 10 mM to 10μM, and thyroxine was shown to be a competitive inhibitor in both cases. On the basis of relative affinities and inhibitory effects, it appears that the order of affinity for the phenolic ring deiodinase is 3,3′,5′-triiodo-l-thyronine-(rT3) > l-thyroxine(T4) > 3,4,3′-triido-l-thyronine(T3), whereas for the nonphenolic ring deiodinase the order is T3 > T4 > rT3. Diiodotyrosine did not affect their deiodination. 相似文献
12.
John R. Arthur Fergus Nicol Geoffrey J. Beckett 《Biological trace element research》1992,33(1-3):37-42
Selenium deficiency impairs thyroid hormone metabolism by inhibiting the synthesis and activity of the iodothyronine deiodinases,
which convert thyroxine (T4) to the more metabolically active 3,3′-5 triiodothyronine (T3). Hepatic type I iodothyronine deiodinase, identified in partially purified cell fractions using affinity labeling with [125I]N-bromoacetyl reverse triiodothyronine, is also labeled with75Se by in vivo treatment of rats with75Se-Na2SeO3. Thus, the type I iodothyronine 5′-deiodinase is a selenoenzyme. In rats, concurrent selenium and iodine deficiency produces
greater increases in thyroid weight and plasma thyrotrophin than iodine deficiency alone. These results indicate that a concurrent
selenium deficiency could be a major determinant of the severity of iodine deficiency. 相似文献
13.
《Comparative biochemistry and physiology. A, Comparative physiology》1979,62(2):295-300
- 1.1. Three days of starvation depressed the T4 (l-thyroxine) levels in plasma and the T4 degradation rate (DR) in 1-yr-old rainbow trout acclimated at 11–12°C, but had little effect on the plasma T3 (3,5,3'-triiodo-l-thyronine) levels or T3DR.
- 2.2. The depression in T4DR was accompanied by decreased T4 deiodination and decreased conversion of T4 to T3, but there was little change in T4 biliary excretion.
- 3.3. T3 kinetics differed from T4 kinetics in suggesting more rapid fractional exchange of T3 between “plasma” and “tissue” compartments.
- 4.4. In contrast to T4, T3 underwent negligible deiodination.
14.
Seiji Ichida Tetsuyuki Wada Kiyo Hashimoto Yasunari Kasamatsu Takafumi Akimoto Miki Tahara 《Neurochemical research》1996,21(6):675-680
Specific binding and specific labeling of125I-ω-CgTX were investigated in crude membranes from both subfractionated fractions and various brain areas in chick whole brain.
The specific activities of the marker enzymes 2′,3′-cyclic nucleotide 3′-phosphorylase, Na/K ATPase and succinic dehydrogenase
in the subfractionated fractions were three- to five-fold higher than those in the P2 fraction. However, the amount of specific [125I]ω-CgTX binding in the fractions of synaptosomes and synaptic plasma membranes was only about 1.2-times higher than that
in the P2 fraction. The characteristics of specific125I-ω-CgTX labeling with disccinimidyl suberate to the 135-kDa band were generally comparable to those of specific [125I]ω-CgTX binding sites. These results suggest that the specific binding sites of [125I]ω-CgTX were not localized the synaptosomes and synaptic plasma membranes fractions, although each fraction was well isolated
from the others from which were decided by the strength of specific activity for marker enzymes. 相似文献
15.
The total mitochondrial fraction of bovine corpus luteum specifically bound [3H]prostaglandin (PG) E1, [3H] PGF2α, and 125I-labeled human lutropin (hLH) despite very little 5′-nucleotidase activity, a marker for plasma membranes. Since the total mitochondrial fraction isolated by conventional centrifugation techniques contains both mitochondria and lysosomes, it was subfractionated into mitochondria and lysosomes to ascertain the relative contribution of these fractions to the binding. Subfractionation resulted in an enrichment of cytochrome c oxidase (a marker for mitochondria) in mitochondria and of acid phosphatase (a marker for lysosomes) in lysosomes. The lysosomes exhibited little or no contamination with Golgi vesicles, rough endoplasmic reticulum, or peroxisomes as assessed by their appropriate marker enzymes. Subfractionation also re ulted in [3H] PGE1, [3H] PGF2α, and 125I-labeled hLH binding enrichment with respect to homogenate in lysosomes but not in mitochondria. The lysosomal binding enrichment and recovery were, however, lower than in plasma membranes. The ratios of marker enzyme to binding, an index of organelle contamination, revealed that plasma membrane and lysosomal receptors were intrinsic to these organelles. Freezing and thawing had markedly increased lysosomal binding but had no effect on plasma membrane binding. Exposure to 0.05% Triton X-100 resulted in a greater loss of plasma membrane compared to lysosomal binding. In summary, the above results suggest that lysosomes, but not mitochondria, in addition to plasma membranes, intrinsically contain receptors for PGs and gonadotropins. Furthermore, lysosomes overall contain a greater number of PGs and gonadotropin receptors compared to plasma membranes and these receptors are associated with the membrane but not the contents of lysosomes. 相似文献
16.
Thomas W. R?sler Andreas Matusch Damiano Librizzi Oscar Arias-Carrión Nils Freundlieb Helmut Hoeffken Wolfgang H. Oertel Candan Depboylu Günter U. H?glinger 《PloS one》2014,9(7)
With the aim to develop beneficial tracers for cerebral tumors, we tested two novel 5-iodo-2′-deoxyuridine (IUdR) derivatives, diesterified at the deoxyribose residue. The substances were designed to enhance the uptake into brain tumor tissue and to prolong the availability in the organism. We synthesized carrier added 5-[125I]iodo-3′,5′-di-O-acetyl-2′-deoxyuridine (Ac2[125I]IUdR), 5-[125I]iodo-3′,5′-di-O-pivaloyl-2′-deoxyuridine (Piv2[125I]IUdR) and their respective precursor molecules for the first time. HPLC was used for purification and to determine the specific activities. The iodonucleoside tracer were tested for their stability against human thymidine phosphorylase. DNA integration of each tracer was determined in 2 glioma cell lines (Gl261, CRL2397) and in PC12 cells in vitro. In mice, we measured the relative biodistribution and the tracer uptake in grafted brain tumors. Ac2[125I]IUdR, Piv2[125I]IUdR and [125I]IUdR (control) were prepared with labeling yields of 31–47% and radiochemical purities of >99% (HPLC). Both diesterified iodonucleoside tracers showed a nearly 100% resistance against degradation by thymidine phosphorylase. Ac2[125I]IUdR and Piv2[125I]IUdR were specifically integrated into the DNA of all tested tumor cell lines but to a less extend than the control [125I]IUdR. In mice, 24 h after i.p. injection, brain radioactivity uptakes were in the following order Piv2[125I]IUdR>Ac2[125I]IUdR>[125I]IUdR. For Ac2[125I]IUdR we detected lower amounts of radioactivities in the thyroid and stomach, suggesting a higher stability toward deiodination. In mice bearing unilateral graft-induced brain tumors, the uptake ratios of tumor-bearing to healthy hemisphere were 51, 68 and 6 for [125I]IUdR, Ac2[125I]IUdR and Piv2[125I]IUdR, respectively. Esterifications of both deoxyribosyl hydroxyl groups of the tumor tracer IUdR lead to advantageous properties regarding uptake into brain tumor tissue and metabolic stability. 相似文献
17.
Sean R. Donohue Katarina Varnäs Zhisheng Jia Balázs Gulyás Victor W. Pike Christer Halldin 《Bioorganic & medicinal chemistry letters》2009,19(21):6209-6212
There is strong interest to study the involvement of brain cannabinoid subtype-1 (CB1) receptors in neuropsychiatric disorders with single photon emission computed tomography (SPECT) and a suitable radioligand. Here we report the synthesis of a novel high-affinity radioiodinated CB1 receptor ligand ([125I]8, [125I]1-(2-iodophenyl)-4-cyano-5-(4-methoxyphenyl)-N-(piperidin-1-yl)-1H-pyrazole-3-carboxylate, [125I]SD7015). By autoradiography in vitro, [125I]8 showed selective binding to CB1 receptors on human brain postmortem cryosections and now merits labeling with iodine-123 for further evaluation as a SPECT radioligand in non-human primate. 相似文献
18.
《International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology》1987,14(5):511-514
Various parameters of thyroid function were studied in 27 rabbits, out of which 10 were immunized to produce antibodies against triiodothyronine (T3), 9 against thyroxine (T4) and 8 were normals. Estimations of T3, T4, Free T4 (FT4) and thyrotropin (TSH) in blood, qualitative and quantitative analysis of iodoamino acids in serum, protein bound iodine-131 (PB131I), butanol extractable iodine-125 (BE125I) and measurement of the disappearance rates of 125I-labelled T3 and T4 from plasma were done. In addition, glandular changes were also studied by measurement of 131I uptake, thyroid scanning and chromatographic analysis of hydrolysate of soluble iodoproteins. In T3 immunized animals, levels of T3 in serum increased by 38 to 125 times, levels of TSH also showed a significant rise (7.4 ± 1.2 vs 28 ± 9 ng/mL). Chromatographic analysis of iodoamino acids in serum as well as in the hydrolysate of the thyroid gland demonstrated a selective increase in synthesis of T3. Rate of disappearance of T3 from blood showed a significant decline. Thyroid glands in the immunized rabbits showed signs of hypertrophy and hyperplasia. Identical studies done in rabbits immunized to produce antibodies against T4 showed a similar pattern though of variable degree. Our studies indicate that the thyroid glands of the immunized rabbits undergo marked alterations resulting in selective increase in the synthesis and secretion of the particular thyroid hormone against which they were immunized. They do so under the influence of increased levels of TSH. 相似文献
19.
The role of selenium in thyroid hormone metabolism and effects of selenium deficiency on thyroid hormone and iodine metabolism 总被引:1,自引:0,他引:1
John R. Arthur Fergus Nicol Geoffrey J. Beckett 《Biological trace element research》1992,34(3):321-325
Selenium deficiency impairs thyroid hormone metabolism by inhibiting the synthesis and activity of the iodothyronine deiodinases,
which convert thyroxine (T4) to the more metabolically active 3,3′–5 triiodothyronine (T3). Hepatic type I iodothyronine deiodinase, identified in partially purified cell fractions using affinity labeling with [125I]N-bromoacetyl reverse triiodothyronine, is also labeled with75Se by in vivo treatment of rats with75Se−Na2SeO3. Thus, the type I iodothyronine 5′-deiodinase is a selenoenzyme. In rats, concurrent selenium and iodine deficiency produces
greater increases in thyroid weight and plasma thyrotrophin than iodine deficiency alone. These results indicate that a concurrent
selenium deficiency could be a major determinant of the severity of iodine deficiency. 相似文献
20.
《International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology》1992,19(6):627-637
A significant retention of [125I]triiodothyronine ([125I]T3) in the retrobulbar orbital area of mice has been previously shown. The present study was initiated to determine tissue and intracellular localization of the thyroid hormone in the above area which is concerned in human Graves' disease of the thyroid.Male and female Balb C mice were intravenously injected with 0.1 mL of [125I]T3 (0.2 mCi/gmg). At various time intervals (30 s-10 min) the animals were sacrificed, bled and periorbital tissues were isolated under a dissecting microscope. Three series of samples were prepared: (a) frozen samples for cryomicrotome sections, (b) samples fixed in 10% formaldehyde for paraffin embedded tissues and (c) samples fixed in paraformaldehyde (2%), glutaldehyde (2%) and 0.1 M sodium cacodylate for embedding in Epon-Araldite-DDSA. Sections 5 μ m and 400–600 Å thick for light and electron microscopy, respectively, were coated with Ilford L4 emulsion and exposed for 9–21 days. Light microscope autoradiography demonstrated that [125I]T3 injected intravenously is rapidly transported in the cells of fat tissue of the peribulbar orbital area and tissues with glandular or muscular function: the hormone showed a high affinity for the intra- and extraorbital lacrymal gland cells, the cells of the Harder's gland, those of the sebaceous and meibomian glands of the eye-lids, as well as for local muscular structures. Electron microscope autoradiography showed that radioactivity is already localized inside the cells 30 s after the i.v. injection of [125I]T3 and it is distributed throughout the cytoplasm, with a higher concentration in the vesicles of the Harder's gland cells (rich in lipids and porphyrin), in the endoplasmic reticulum and the mitochondria of the lacrymal glands. 10 min after injection, a shifting of the radioactivity towards the nucleus area was observed. In conclusion, after vivo injection, the thyroid hormone rapidly penetrates the cells of fat glandular and muscular tissues in the orbital area. Intracellularly, the affinity of the hormone for the secretory vesicles, rough endoplasmic reticulum, mitochondria and nucleus suggest that T3 could play a role in secretory and metabolic functions of the tissues in the retrobulbar orbital area. 相似文献