The role of selenium in thyroid hormone metabolism and effects of selenium deficiency on thyroid hormone and iodine metabolism

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.     

Conversion and binding of tetraiodothyronine in developing rat brain

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.     

The role of selenium in thyroid hormone metabolism and effects of selenium deficiency on thyroid hormone and iodine metabolism

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.     

Increased β<Subscript>2</Subscript>-Adrenergic Receptor Activity by Thyroid Hormone Possibly Leads to Differentiation and Maturation of Astrocytes in Culture

Summary (1) Our earlier studies indicate a downsteam regulatory role of the β-adrenergic receptor (β-AR) system in thyroid hormone induced differentiation and maturation of astrocytes. In the present study we have investigated the contributions of the subtypes of β-AR in the above phenomenon. (2) Primary astrocyte cultures were grown under thyroid hormone deficient as well as under euthyroid conditions. [¹²⁵I]Pindolol ([¹²⁵I]PIN) binding studies showed a gradual increase in the specific binding to β₂-AR when observed at 5, 10, 15, and 20 days under both cultural conditions. Thyroid hormone caused an increase in binding of [¹²⁵I]PIN to β₂-AR compared to thyroid hormone deficient controls at all ages of astrocyte culture. (3) Saturation studies using [¹²⁵I]PIN in astrocyte membranes prepared from 20-day-old cultures showed a significant increase in the affinity of the receptors (K _D) in the thyroid hormone treated cells without any change in receptor number (B _max). (4) β₂-AR mRNA levels were measured by real-time PCR during ontogenic development as well as during exposure of 10-day-old hypothyroid cultures to normal levels of thyroid hormone for 2, 6, 12, and 24 h. None of the conditions caused any significant change in the β₂-adrenergic receptor mRNA levels when compared with corresponding hypothyroid controls. (5) Over expression of β₂-AR cDNA in hypothyroid astrocytes caused morphological transformation in spite of the absence of thyroid hormone in the medium. (6) Taken together, results suggest thyroid hormone causes a selective increase in [¹²⁵I]PIN binding to β₂-AR due to increase in receptor affinity, which may lead to maturation of astrocytes.     

Influence of short-term oestradiol treatment on plasma thyroid hormone kinetics in rainbow trout, Salmo gairdneri

The effects of 17β-oestradiol (E₂) on plasma kinetics of thyroid hormones (T₄, l-thyroxine; T₃, 3,5,3′-triiodo-l-thyronine) were studied in immature rainbow trout. E₂-3-benzoate (0.5 mg/100 g) was injected intraperitoneally on days 0 and 3, and on the morning of day 4 each trout received an intracardiac injection of either [¹²⁵I]T₄ and Na ¹³¹I or [^I25I]T₃. Groups of trout were bled and killed from 5 min to 4 days post-injection of tracer. E₂ did not alter the plasma T₄ level but depressed the T₄ plasma clearance rate, plasma-to-total tissue flux of T₄ and thyroidal T₄ secretion rate. Monodeiodination of T₄ to T₃ was also depressed, as judged from plasma [^I25I]T₃ and ^I25I ^? levels in [¹²⁵I]T₄-injected trout. E₂ had no major effect on T₃ plasma clearance rate but depressed the plasma T₃ level, plasma-to-total tissue flux of T₃ and the T₃ plasma appearance rate. E₂ had no influence on biliary transport of [^I25I]T₄ or [¹²⁵I]T₃. The above results suggest that E₂, at the dose range employed, depresses extrathyroidal T₄ to T₃ conversion, which may in turn decrease plasma T₄ clearance and thyroidal T₄ secretion.     

The effect of propylthiouracil on thyroid-stimulating hormone-induced alterations in iodothyronine secretion from perfused dog thyroids

The aim of this study was to see whether the inhibitory effect of propylthiouracil on thyroidal secretion of 3,5,3′-triiodothyronine (T₃) and 3,3′,5′-triiodothyronine (rT₃) could be reproduced in intensively stimulated thyroids, and to elucidate whether an increase in the fractional deiodination of thyroxine (T₄) to T₃ and rT₃ during iodothyronine secretion might be responsible for the transient fall in the T₄/T₃ and T₄/rT₃ ratios in thyroid secretion seen in the early phase after stimulation of thyroid secretion.For this purpose T₄, T₃ and rT₃ were measured in effluent from isolated dog thyroid lobes perfused in a non-recirculation system using a synthetic hormone free medium. 1 mmol/l propylthiouracil induced a significant reduction in thyroid-stimulating hormone (TSH) stimulated T₃ and rT₃ release while the release of T₄ was unaffected. This supports our previous conclusion that T₄ is partially monodeiodinated to T₃ and rT₃ during thyroid secretion. Infusion of 1 mmol/l propylthiouracil for 30 min or 3 mmol/l propylthiouracil for 120 min did not abolish the transient fall in effluent T₄/T₃ and T₄/rT₃ induced by TSH stimulation. Thus, this phenomenon seems not to depend on intrathyroidal iodothyromine deiodinating processes.     

Tissue localization of [125I]triiodothyronine in the periorbital area of mice: a microautoradiographic study

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.     

The interaction of radioiodinated thyrotropin with plasma membranes: Evidence for high affinity binding sites in the thyroid

The binding of biologically active [¹²⁵I]thyrotropin to purified plasma membranes prepared from bovine thyroid glands was studied. At 4°C, specific binding reached a maximum after 2 h of incubation and a plateau was maintained for up to 20 h. Degradation of [¹²⁵I]thyrotropin was undetectable after 2 h of incubation and was only 10% of the total after 20 h.At pH 6.0, at which binding was maximal, a single class of binding sites, having a dissociation constant of approx. 25 nM, was evident. Dissociation studies revealed first order kinetics with a half-time of 2–3 min. At pH 7.5, binding curves were complex, suggesting two orders of binding sites with dissociation constants of approx. 200 nM and 80 pM. Further, at this pH, dissociation of the thyrotropin from its receptor was also complex, suggesting the presence of two first order reactions, one with a half-time similar to that seen at pH 6.0 and another with a half-time of 4 h. At both pH 6.0 and 7.5, insulin, glucagon, growth hormone, and prolactin were without effect on [¹²⁵I]thyrotropin binding.Similar high affinity and low affinity binding sites were seen with porcine thyroid membranes, but only low affinity sites were seen with either rat liver membranes or human cultured lymphocytes.     

Thyroid function and thyrotropin levels in rabbits immunized to produce antibodies against thyroid hormones

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.     

Effect of selenium on thyroid hormone metabolism in filial cerebrum of mice with excessive iodine exposure

The effects of supplementing selenium on thyroid hormone metabolism were studied on mice with excessive iodine exposure. The serum concentrations of thyroxine (T₄) and triiodothyronine (T₃) and the activities of iodothyronine 5′ and 5-deiodinase (D2, D3) were measured in the brain of filial mice to study the influence of selenium on thyroid hormone metabolism. Measurements were carried out on postnatal day 0, 14, and 28. It was found that selenium supplementation alleviated the adverse effects of excessive iodine on progeny. The serum TT₄ level as well as TT₄ and TT₃ concentrations and D3 activity in cerebrum of progeny decreased, whereas D2 activity increased in the cerebrum of progeny on postnatal day 0 and 14. Selenium supplementation exerted some favorable effects on thyroid hormone metabolism in cerebrum of progeny of dam with excessive iodine intake.     

Species differences and mechanism of action of A<Subscript>3</Subscript> adenosine receptor allosteric modulators

Activity of the A₃ adenosine receptor (AR) allosteric modulators LUF6000 (2-cyclohexyl-N-(3,4-dichlorophenyl)-1H-imidazo [4,5-c]quinolin-4-amine) and LUF6096 (N-{2-[(3,4-dichlorophenyl)amino]quinolin-4-yl}cyclohexanecarbox-amide) was compared at four A₃AR species homologs used in preclinical drug development. In guanosine 5′-[γ-[³⁵S]thio]triphosphate ([³⁵S]GTPγS) binding assays with cell membranes isolated from human embryonic kidney cells stably expressing recombinant A₃ARs, both modulators substantially enhanced agonist efficacy at human, dog, and rabbit A₃ARs but provided only weak activity at mouse A₃ARs. For human, dog, and rabbit, both modulators increased the maximal efficacy of the A₃AR agonist 2-chloro-N ⁶-(3-iodobenzyl)adenosine-5′-N-methylcarboxamide as well as adenosine > 2-fold, while slightly reducing potency in human and dog. Based on results from N ⁶-(4-amino-3-[¹²⁵I]iodobenzyl)adenosine-5′-N-methylcarboxamide ([¹²⁵I]I-AB-MECA) binding assays, we hypothesize that potency reduction is explained by an allosterically induced slowing in orthosteric ligand binding kinetics that reduces the rate of formation of ligand-receptor complexes. Mutation of four amino acid residues of the human A₃AR to the murine sequence identified the extracellular loop 1 (EL1) region as being important in selectively controlling the allosteric actions of LUF6096 on [¹²⁵I]I-AB-MECA binding kinetics. Homology modeling suggested interaction between species-variable EL1 and agonist-contacting EL2. These results indicate that A₃AR allostery is species-dependent and provide mechanistic insights into this therapeutically promising class of agents.     

Binding of thyroid hormones to human hemoglobin and localization of the binding site

Radiolabeled thyroid hormones were allowed to bind to erythrocyte cytosol and the complex was fractionated by Sephadex G-100 or by high-performance liquid chromatography (HPLC). On Sephadex G-100, four radioactive peaks (P₁P₄) were obtained, whereas HPLC gave only three radioactive peaks (P₁P₃). Chromatographic studies with human adult Hb and non-Hb cytosol protein fractions, which had been reacted with radiolabeled thyroid hormones, and immune precipitation with specific antisera for the hormones, confirmed that the first peak of Sephadex G-100 radioactivity was a mixture of Hb and non-Hb proteins, while the second peak was Hb. The third peak was free¹²⁵I and the fourth peak was unbound¹²⁵I-T₃ or¹²⁵I-T₄. The third peak of HPLC was confirmed to be a mixture of free¹²⁵I and unbound radiolabeled thyroid hormones. Scatchard analysis of the interaction between T₄ and apo-Hb, and the - and -chains of human Hb suggested the presence of the specific binding site(s) for the hormone. Interaction between T₄ and synthesized peptides, which constitute the heme pocket of the -chain of Hb (61–75, 71–85, 81–95), indicated that the T₄ binding site of Hb resides within the heme-binding cavity. It is concluded that human erythrocyte cytosol does not contain receptor for thyroid hormones and cannot be a model for studying functions of cytosol receptor for the hormones; rather, it contains binding protein with large binding capacity, including Hb and non-Hb proteins, which possibly constitute a large reservoir for the hormone in blood.     

Stimulation of calcitonin secretion in the pig by calcitonin gene-related peptide

Pig thyroid glands were surgically isolated in situ and perfused with autologous blood to which was added known concentrations of calcitonin gene-related peptide (αCGRP). When thyroids were perfused with measured concentrations of CGRP within the range of 0.6–600 nM, the secretion rate of calcitonin (CT) was stimulated while the release of T₃, T₄, and somatostatin remained unchanged. Specific binding of ¹²⁵I-CGRP to pig thyroid plasma membranes was demonstrated, and binding was inhibited by unlabelled CGRP but not by CT or by other peptides unrelated structurally to CGRP. The findings indicate that the pig thyroid gland contains plasma membrane binding sites for CGRP and that CGRP is capable of stimulating the secretion of CT.     

Subcellular distribution of iodothyronine 5′-deiodinase in cerebral cortex from hypothyroid rats

We have examined iodothyronine deiodination in subcellular fractions of cerebral cortex obtained from hypothyroid rats. Enzymatic activities were measured at 37°C in the presence of 20 mM dithiothreitol with ¹²⁵I-labeled T₄ and ¹²⁵I-labeled rT₃ as substrate for 5′-deiodination and ¹³¹I-labeled T₃ as the substrate for the 5-deiodinase. Reaction products were separated by descending paper and/or ion-exchange chromatography. Cerebral cortex subcellular fractions were also characterized by marker enzyme analysis and electron microscopy. Under optimal reaction conditions more than 80% of the 5′-deiodinase was recovered after fractionation. Both 5′-deiodinase and (Na⁺ +K⁺-ATPase showed similar subcellular distributions and were enriched approx. 3-fold in the easily sedimenting membrane fraction and nerve terminal plasma membranes. Crude microsomal membranes (6·10⁶g·min pellet) also showed 2-fold enrichment of these enzymes. Nuclei and isolated mitochondria were devoid of deiodinating activity. T₄ and T₃ 5-deiodinating activity was absent in the easily sedimenting membranes and present but not enriched in particulate fractions containing microsomal membranes. These data suggest that iodothyronine 5′-deiodinase is associated with plasma membrane fractions in the cerebral cortex.     

Effect of Cold Exposure on Thyroid Hormone Metabolism and Nuclear Binding in Rat Brain

In this study we examined whether adult rat brain tissue (cerebral hemispheres) would under cold exposure respond with changes in the local metabolism and nuclear binding of thyroid hormones (T₃, T₄). Adult, control rats kept at 22°C and cold exposed (4°C, 20 h) rats were injected with trace of ¹²⁵I-T₄ or ¹²⁵I-T₃ returned to their respective environment and sacrificed four hours later. The radioactive hormonal forms were identified and quantified in the cytoplasmic and nuclear fractions. It was found that in cold exposed rats injected with ¹²⁵I-T₄, the total cytoplasmic radioactivity was higher than that of controls. This increase was not associated with ¹²⁵I-T₄ but it reflected an increase (88 %) in its deiodination product ¹²⁵I-T₃ (¹²⁵I-T₃ (T₄)). Although total cytoplasmic ¹²⁵I-T₄ did not change, there was a decrease (28%) in its protein free cytoplasmic fraction. ¹²⁵I-T₃ (T₄) and ¹²⁵I-T₄ bound to the nuclear fraction were found to decrease by 58 and 46% respectively. Cold exposed animals injected with ¹²⁵I-T₃ also showed an increase in cytoplasmic ¹²⁵I-T₃ (81%) and a decrease in ¹²⁵I^– (40%) whereas ¹²⁵I-T₃ bound to the nuclear fraction decreased by 64%. These results indicate that cold exposure of rats decreases brain local T₃ metabolism and nuclear binding while it does not effect local T₄ metabolism.     

Phenolic and nonphenolic ring deiodinations of iodothyronines in cultured hepatocarcinoma cell hemogenate from monkey

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.     

Characterization of Xenopus cytosolic thyroid-hormone-binding protein (xCTBP) with aldehyde dehydrogenase activity

Multiple cytosolic thyroid-hormone-binding proteins (CTBPs) with varying characteristics, depending on the species and tissue, have been reported. We first purified a 59-kDa CTBP from Xenopus liver (xCTBP), and found that it is responsible for major [¹²⁵I]T₃-binding activity in Xenopus liver cytosol. Amino acid sequencing of internal peptide fragments derived from xCTBP demonstrated high identity to the corresponding sequence of mammalian aldehyde dehydrogenases 1 (ALDH1). To confirm whether or not xCTBP is identical to xALDH1, we isolated cDNAs encoding xALDH1 from an adult Xenopus hepatic cDNA library. The amino acid sequences deduced from the two isolated xALDH1 cDNAs were very similar to those of mammalian ALDH1 enzymes. The recombinant xALDH1 protein exhibited both T₃-binding activity and ALDH activity converting retinal to retinoic acid (RA), which were similar to those of xCTBP purified from liver cytosol. The T₃-binding activity was inhibited by NAD, while the ALDH activity was inhibited by thyroid hormones. Our results demonstrate that xCTBP is identical to ALDH1 and suggest that this protein might modulate RA synthesis and intracellular concentration of free T₃. Communications between thyroid hormone and retinoid pathways are discussed.     

Triiodothyronine bound to red blood cells is not available for transport through the blood-brain barrier

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.     

Binding of thyroid hormone by erythrocyte cytoplasmic proteins.

Characteristics of iodothyronine-binding to dog erythrocyte cytosol proteins are described. Half-time of association of both thyroxine (T₄) and triiodothyronine (T₃) is 60 min and equilibrium is achieved at 120 min (20°C). Binding is enhanced at 37°C compared to 20°C. T₄ and T₃ binding capacities of the cytosol are 10 and 5 picomoles/mg cytosol protein, respectively. Gel filtration (G-100) reveals 3 protein fractions that dissociably bind both T₄ and T₃. Quantitative and qualitative differences distinguish the erythrocyte cytosol “receptor” proteins from those previously described in other dog tissues. The erythrocyte is a model for studying functions of cytosol “receptors” for iodothyronines.