The TSH receptor: Structure and interaction with autoantibodies in thyroid disease

1987 ◽  
Vol 116 (1_Suppl) ◽  
pp. S157-S165 ◽  
Author(s):  
J. Furmaniak ◽  
Y. Nakajima ◽  
F. A. Hashim ◽  
F. M. Creagh ◽  
E. Davies Jones ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Thyroid Tissue ◽  
Tsh Receptor ◽  
Sds Page ◽  
Affinity Labelling ◽  
Stokes Radius ◽  
A Subunit ◽  
Receptor Antibodies ◽  
Derivatives Of ◽  
Tsh Receptor Antibodies

Abstract. Studies of the TSH receptor using affinity labelling with photoactive derivatives of TSH and analysis by SDS-PAGE have shown that the receptor contains 2 subunits (A and B), linked by a disulphide bridge. Similar results are obtained with TSH receptors from human, porcine and guinea pig thyroid tissue and from guinea pig fat. Analysis of affinity labelled receptors under non-denaturing conditions suggest that subunits additional to the A and B subunits are not present. Hydrodynamic measurements indicate that the receptor A subunit has an approximately spherical structure (Stokes' radius 70Å) and when this interacts with TSH (an elongated structure with Stokes' radius 56Å) a very elongated complex (Stokes' radius 104Å) is formed. Isoelectric focusing studies of the TSH receptor A subunit, TSH and TSH receptor antibodies indicate that charge-charge interactions are of considerable importance in the binding of hormone and antibody to the receptor.

Isoelectric focusing of the human TSH receptor A subunit

1986 ◽  
Vol 6 (7) ◽  
pp. 685-689 ◽  
Author(s):  
F. A. Hashim ◽  
E. Davies Jones ◽  
R. D. Howells ◽  
B. Rees Smith
Keyword(s):  
Isoelectric Focusing ◽  
Isoelectric Point ◽  
Water Soluble ◽  
Tsh Receptor ◽  
Isoelectric Points ◽  
A Subunit ◽  
Receptor Antibodies ◽  
Tsh Receptor Antibodies ◽  
Charge Interactions

The water soluble A subunit of the human TSH receptor has been shown to have an isoelectric point of 5. As both TSH and TSH receptor antibodies have isoelectric points in the region of 8–10, charge-charge interactions must be of major importance in the binding of hormone or antibody to the TSH receptor A subunit.

Different binding of stimulatory-type and blocking-type TSH receptor antibody with guinea-pig testis membrane

1991 ◽  
Vol 125 (5) ◽  
pp. 563-569 ◽  
Author(s):  
T. Inui ◽  
Y. Ochi ◽  
T. Hachiya ◽  
W. Chen ◽  
Y. Nakajima ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Inhibitory Effect ◽  
Primary Hypothyroidism ◽  
Significant Inhibition ◽  
Tsh Receptor ◽  
Α Subunit ◽  
Blocking Antibody ◽  
Thyroid Stimulating Antibody ◽  
Receptor Antibodies ◽  
Tsh Receptor Antibodies

Abstract. A receptor assay using [125I]bTSH-binding to guinea-pig testis membrane was developed. Unlabelled hCG and FSH inhibited [125I]bTSH binding. In patients with Graves' disease and in untreated hyperthyroid patients, almost all long-acting thyroid stimulators and thyroid-stimulating antibodies, respectively did not inhibit [125I]bTSH binding, which on the other hand was inhibited by thyroid stimulation blocking antibodies in patients with primary hypothyroidism. When the inhibitory effect on the binding of [125I]hCG and 125I-synthetic α-subunit peptide (α26-46) of hCG to testis membrane was examined, bTSH resulted in a significant inhibition. However, all three kinds of TSH receptor antibodies had no inhibitory effect. This study demonstrated 1. interaction of α-subunit of TSH and hCG with the testicular receptor; 2. binding of thyroid stimulation-blocking antibody and lack of binding of thyroid-stimulating antibody to the testicular TSH receptor in spite of binding of these TSH receptor antibodies to the thyroidal TSH receptor, and 3. lack of binding of thyroid-stimulating antibody and thyroid stimulation-blocking antibody to the testicular gonadotropin receptor.

TSH Receptor Antibodies

Thyroid ◽  
2007 ◽  
Vol 17 (10) ◽  
pp. 923-938 ◽  
Author(s):  
Bernard Rees Smith ◽  
Jane Sanders ◽  
Jadwiga Furmaniak
Keyword(s):  
Tsh Receptor ◽  
Receptor Antibodies ◽  
Tsh Receptor Antibodies

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

1989 ◽  
Vol 120 (1) ◽  
pp. 99-106 ◽  
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.

Anti-TSH receptor antibodies in Graves' disease modulate the kinetic behaviour of autologous thyroid TSH receptors. Evidence of the IgG-induced cross-linkage of autologous TSH receptors

1984 ◽  
Vol 105 (3) ◽  
pp. 330-340 ◽  
Author(s):  
Tjerk W. A. de Bruin ◽  
Daan van der Heide ◽  
Maria C. Krol
Keyword(s):  
Binding Sites ◽  
Plasma Membranes ◽  
Tsh Receptor ◽  
Human Thyroid ◽  
Graves Disease ◽  
Kinetic Behaviour ◽  
High Affinity ◽  
Cross Linkage ◽  
Receptor Antibodies ◽  
Tsh Receptor Antibodies

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.

TSH-receptor antibodies

Thyrotropin ◽  
1987 ◽  
pp. 307-314 ◽  
Author(s):  
P. Vitti ◽  
G. F. Fenzi ◽  
L. Chiovato ◽  
C. Marcocci ◽  
A. Pinchera
Keyword(s):  
Tsh Receptor ◽  
Receptor Antibodies ◽  
Tsh Receptor Antibodies
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