Thyroglobulin and Thyroid Hormone Release after Intravenous Administration of Bovine Thyrotropin in Man*

Unger, Jonathan; Heuverswyn, Brigitte Van; Decoster, Christine Gervy; Cantraine, Francis; Mockel, Jean; Herle, Andre Van

doi:10.1210/jcem-51-3-590

Cited by 51 publications

(24 citation statements)

References 16 publications

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“…This was unexpected considering previous studies in human (4)(5)(6) and in rat (15,16) suggesting that Tg released by the stimulated thyroid gland would mainly correspond to iodinated Tg molecules, thus originating from the lumen of thyroid follicles. From physicochemical analyses of serum Tg by velocity sedimentation on sucrose gradients and Western blotting (9), we recently proposed a pathway of Tg release that could explain the lack of T3 and T4 residues on serum Tg from patients with GD.…”

Section: Figurecontrasting

confidence: 60%

“…Secondly, iodinated Tg molecules (with hormones residues) internalized at the apical pole of thyrocytes from the follicle lumen could undergo a transcellular vesicular transport or transcytosis (3) to be released into the extrafollicular fluid. The elevation of serum Tg concentration in response to thyroid stimulation by thyrotropin (TSH) (4,5), or by anti-TSH receptor stimulating antibodies (6) in patients with Graves' disease (GD), could result from the activation of either of these pathways, or both of them. In pathological situations leading to morphological alterations of the thyroid parenchyma, as seems to be the case in subacute thyroiditis (ST), the appearance of Tg in the blood stream might result from the leakage of Tg from disrupted thyroid follicles.…”

Section: Introductionmentioning

confidence: 99%

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Identification of thyroid hormone residues on serum thyroglobulin: a clue to the source of circulating thyroglobulin in thyroid diseases

et al. 1999

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Thyroglobulin (Tg) present in the serum of normal individuals and patients with thyroid disorders could be partly newly synthesized non-iodinated Tg and partly Tg containing iodine and hormone residues originating from the lumen of thyroid follicles. With the aim of examining the contribution of the latter source of Tg to the elevation of serum Tg concentration in thyroid pathophysiological situations, we devised a procedure to identify thyroxine (T4) and tri-iodothyronine (T3) residues on Tg from unfractionated serum. A two-step method, based on (i) adsorption of Tg on an immobilized antihuman Tg (hTg) monoclonal antibody (mAb) and (ii) recognition of hormone residues on adsorbed Tg by binding of radioiodinated anti-T4 mAb and anti-T3 mAb, was used to analyze serum Tg from patients with either Graves' disease (GD), subacute thyroiditis (ST) or metastatic differentiated thyroid cancer (DTC). Purified hTg preparations with different iodine and hormone contents were used as reference. Adsorption of purified Tg and serum Tg on immobilized anti-hTg mAb ranged between 85 and 90% over a wide concentration range. Labeled anti-T4 and anti-T3 mAbs bound to adsorbed purified Tg in amounts related to its iodine content. Tg adsorbed from six out of six sera from ST exhibited anti-T4 and anti-T3 mAb binding activities. In contrast, significant mAb binding was only observed in one out of eight sera from untreated GD patients and in 1 out of 13 sera from patients with DTC. The patient with DTC, whose serum Tg contained T4 and T3, represented a case of hyperthyroidism caused by a metastatic follicular carcinoma. In conclusion, we have identified, for the first time, T4 and T3 residues on circulating Tg. The presence of Tg with hormone residues in serum is occasional in GD and DTC but is a common and probably distinctive feature of ST.

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Section: Figurecontrasting

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Identification of thyroid hormone residues on serum thyroglobulin: a clue to the source of circulating thyroglobulin in thyroid diseases

et al. 1999

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“…Therefore TSH stimulated Tg mRNA level, Tg synthesis and apical Tg exocytosis with the same ratio (threefold) and transiently basal Tg secretion. These results correlate with data obtained by in vivo studies on circulating Tg which appeared to be increased for a short time in human serum after TSH injections (Unger et al, 1980). TSH controlled these steps of Tg expression through the adenylcyclase activation (Chabaud et al, 1988;Chambard et al, 1990).…”

Section: Polarized Secretion Of Tg Relation With the Tg Gene Expresssupporting

confidence: 88%

Hormonogenesis in thyroid cells cultured on porous bottom chambers

et al. 1992

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Different processes implied in thyroid hormonogenesis (thyroglobulin, thyroperoxidase and hydrogen peroxide generating system expressions) and their regulation by TSH and iodide have been studied using porcine thyroid cells cultured in porous bottomed chambers. This system allowed to reproduce the functional bipolarity. Cells form a tight and polarized monolayer. Both apical and basolateral poles of epithelial cells were independently accessible and the cell layer separated two compartments which can contain different media. A major polarized secretion of thyroglobulin into the apical compartment was observed; it was increased in the presence of TSH as well as the thyroglobulin synthesis and mRNA level. These TSH effects were the consequence of adenylcyclase stimulation. Active transport of iodide, iodination of thyroglobulin and hormonosynthesis took place only in the presence of TSH. These steps occurred at the apical pole of cells. In the culture chamber system, thyroglobulin was weakly iodinated (6 atoms of iodide per mole of thyroglobulin; in vivo up to 40 atoms per mole) but hormonogenesis efficiency was close to this one observed in vivo (40%). Iodide concentrations higher than 0.5 microM daily added to the basal medium inhibited iodination of thyroglobulin and hormonosynthesis. Some components contained in culture media were inhibitors for iodination when they were present in the apical medium such as vitamins, amino acids and phenol red. The culture system appears to be interesting for pharmacological and toxicological studies.

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“…This result suggests that the Tg molecules secreted through apical and basal membranes follow different intracellular pathways which probably have different sensitivities to TSH. In contrast, circulating Tg studied on euthyroid human volunteers Unger et al, 1980) appears stimulated by TSH. After an i.v.…”

Section: Tg Transcytosis and Polarized Tg Secretionmentioning

confidence: 84%

Synthesis and apical and basolateral secretion of thyroglobulin by thyroid cell monolayers on permeable substrate: Modulation by thyrotropin

Chambard

Mauchamp

Chabaud

1987

Journal Cellular Physiology

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In the thyroid glands, thyroglobulin (Tg) is specifically synthesized by follicular cells and then secreted into the apical lumen where it is concentrated and used as a substrate for thyroid hormone synthesis. The presence of Tg in the circulation has been reported in normal and pathological situations. To determine the domains of the plasma membrane, apical and/or basolateral, involved in Tg secretion, porcine thyroid epithelial cells were cultured as a monolayer on the porous bottom of a culture chamber in which both apical and basal media are independently accessible. Control experiments using labeled Tg ascertained the tightness of the monolayer and showed that within 48 h only 0.2-0.5% of the Tg introduced in the apical medium was transferred through the cell layer into the basal compartment. For kinetic studies of Tg synthesis and secretion, monolayers were cultured for up to 72 h in the presence of 35S-methionine and with or without 100 microU/ml thyrotropin (TSH) in the basal medium. Labeled Tg was measured by double immunoprecipitation and by fluorography of polyacrylamide gel electrophoresis. We showed that 80-95% of total secreted Tg was recovered in the apical medium. The remainder was secreted through the basolateral membranes in the basal medium. The amount of tg secreted into the apical compartment was stimulated two- to threefold by TSH whereas no TSH effect was observed on secretion in the basal compartment. Moreover, measuring apical and basal volumes, we observed a net water flow from the apical to the basal side. It was stimulated threefold by TSH, increasing the Tg concentration in the apical compartment of the stimulated cell layer. During the culture time, the amount of Tg synthesized and secreted was increased by TSH, as was the Tg mRNA content, as determined by the dot-blot hybridization method.

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Thyroglobulin and Thyroid Hormone Release after Intravenous Administration of Bovine Thyrotropin in Man*

Cited by 51 publications

References 16 publications

Identification of thyroid hormone residues on serum thyroglobulin: a clue to the source of circulating thyroglobulin in thyroid diseases

Identification of thyroid hormone residues on serum thyroglobulin: a clue to the source of circulating thyroglobulin in thyroid diseases

Hormonogenesis in thyroid cells cultured on porous bottom chambers

Synthesis and apical and basolateral secretion of thyroglobulin by thyroid cell monolayers on permeable substrate: Modulation by thyrotropin

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