In Vivo Effects of TSH, TSH-Receptor Antibodies, and Interferon-α-2b in Xenografted Human Thyroid Carcinoma

Abstract. The effect of the anti-TSH receptor antibodies present in the sera of 8 patients with Graves' disease on the affinity constant (Ka) and the number (R) of TSH receptors in autologous human thyroid plasma membranes was investigated. Kinetic analysis of [125I]bTSH binding to human thyroid plasma membranes in the presence of autologous Graves' and normal gammaglobulins was carried out by means of a computer fitting programme. Analysis of the TSH-TSH receptor interaction in the presence of TSH alone yielded curvilinear Scatchard plots, indicating the existence of two independent classes of binding sites (high affinity Ka: 8.5 ± 4.8 × 108 m−1; low affinity Ka: 5.3 ± 2.7 × 106 m−1). Similarly the Scatchard plot for this interaction in the presence of normal gammaglobulins is also curvilinear. Linear Scatchard plots, indicating the existence of only one class of high affinity TSH binding sites (Ka: 3.5 ± 1.8 × 108 m−1), were obtained for both autologous gammaglobulins and pure IgG from 8 patients with Graves' disease. The number of high affinity TSH binding sites in the presence of Graves' gammaglobulins had increased on the average by a factor 3.76 ± 0.74 (sd) with respect to the number found in the presence of normal gammaglobulins. This marked change in the kinetic behaviour of the TSH binding sites provided evidence that there is a direct interaction between anti-TSH receptor antibodies and autologous TSH receptors. Divalency of Graves' IgG or linkage of Fab fragments by anti-Fab antiserum proved to be necessary to produce this specific change in the kinetic behaviour of TSH binding sites. Graves' IgG monovalent Fab and Fc fragments had no effect. We suggest that the mechanism by which anti-TSH receptor antibodies in Graves' disease mimick the biological action of TSH is the IgG-induced cross-linkage of TSH receptors.

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A water-soluble fragment of the thyroid-stimulating hormone receptor which binds both thyroid-stimulating hormone and thyroid-stimulating hormone receptor antibodies

Journal of Endocrinology ◽

10.1677/joe.0.1000113 ◽

1984 ◽

Vol 100 (1) ◽

pp. 113-118 ◽

Cited By ~ 15

Author(s):

E. Davies Jones ◽

B. Rees Smith

Keyword(s):

Hormone Receptor ◽

Gel Filtration ◽

Thyroid Stimulating Hormone ◽

Water Soluble ◽

Tsh Receptor ◽

Human Thyroid ◽

Freezing And Thawing ◽

Receptor Antibodies ◽

Tsh Receptor Antibodies ◽

Stimulating Hormone

ABSTRACT Previous studies have shown that freezing and thawing of human thyroid homogenates releases a water-soluble substance which reversibly binds to TSH-receptor antibodies. This substance has been designated long-acting thyroid stimulator absorbing activity (LAA). We now describe a new method for measuring LAA based on the TSH-receptor assay and application of the technique to the study of LAA. Our results indicate that LAA is a heat-labile glycoprotein which co-elutes with haemoglobin on gel filtration. Furthermore, LAA is retarded by columns of Sepharose–TSH but not by Sepharose coupled to human chorionic gonadotrophin, normal immunoglobulin G or bovine serum albumin, suggesting that LAA contains a binding site for TSH as well as for TSH-receptor antibodies. It would seem therefore that LAA is a water-soluble fragment of the TSH receptor possibly resulting from proteolytic cleavage of the receptor at a site close to the cell surface. J. Endocr. (1984) 100, 113–118

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TSH Receptor Antibodies

Thyroid ◽

10.1089/thy.2007.0239 ◽

2007 ◽

Vol 17 (10) ◽

pp. 923-938 ◽

Cited By ~ 89

Author(s):

Bernard Rees Smith ◽

Jane Sanders ◽

Jadwiga Furmaniak

Keyword(s):

Tsh Receptor ◽

Receptor Antibodies ◽

Tsh Receptor Antibodies

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Bioassays for TSH Receptor Antibodies: Quo Vadis?

European Thyroid Journal ◽

10.1159/000375445 ◽

2015 ◽

Vol 4 (1) ◽

pp. 3-5 ◽

Cited By ~ 21

Author(s):

George J. Kahaly

Keyword(s):

Tsh Receptor ◽

Quo Vadis ◽

Receptor Antibodies ◽

Tsh Receptor Antibodies

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Inhibition of thyrotropin-stimulated adenylate cyclase activation and growth of rat thyroid cells, FRTL-5, by immunoglobulin G from patients with primary myxedema: comparison with activities of thyrotropin-binding inhibitor immunoglobulins

Acta Endocrinologica ◽

10.1530/acta.0.1200099 ◽

1989 ◽

Vol 120 (1) ◽

pp. 99-106 ◽

Cited By ~ 17

Author(s):

B. Y. Cho ◽

Y. K. Shong ◽

H. K. Lee ◽

C.-S. Koh ◽

H. K. Min

Keyword(s):

Hashimoto’S Thyroiditis ◽

Thymidine Incorporation ◽

Tsh Receptor ◽

Hashimoto's Thyroiditis ◽

Thyroid Cells ◽

Rat Thyroid ◽

Receptor Antibodies ◽

Tsh Receptor Antibodies ◽

Growth Inhibiting ◽

Blocking Type

Abstract. We studied the blocking type TSH receptor antibodies in 28 patients with primary myxedema and 21 patients with goitrous Hashimoto's thyroiditis by measuring the ability of their IgGs to inhibit TSH binding to its receptor, and to inhibit TSH-stimulated cAMP increase and [3H] thymidine incorporation in a rat thyroid cell line, FRTL-5. The incidences of TSH binding inhibitor immunoglobulin, thyroid stimulation inhibiting immunoglobulin and thyroid growth inhibiting immunoglobulin in patients with primary myxedema were 54.6, 75 and 65.2%, respectively, against 14.3,0 and 17.7%, respectively, in goitrous Hashimoto's thyroiditis. The antibodies inhibited dose-dependently not only TSH stimulated but also Graves' IgG-stimulated cAMP increase and [3H] thymidine incorporation. The TSH binding inhibitor immunoglobulin activities in patients with primary myxedema were significantly correlated with both the thyroid stimulation inhibiting immunoglobulin (r = 0.665; P<0.01) and the thyroid growth inhibiting immunoglobulin (r = 0.618; P<0.01) activity. Thirteen patients whose TSH binding inhibitor immunoglobulin activities were more than 50% had both strong thyroid stimulation inhibiting immunoglobulin (75.1–100%) and thyroid growth inhibiting immunoglobulin (57.4–100%) activities. These data suggest that the vast majority of patients with primary myxedema have potent blocking type TSH receptor antibodies. These might play a role in primary myxedema causing hypothyroidism and thyroid atrophy through inhibiting TSH-stimulated cAMP generation.

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