TSH receptor antibodies do not alter the function of gonadotropin receptors stably expressed in eukaryotic cells

Massimo Tonacchera, Eleonora Ferrarini, Antonio Dimida, Patrizia Agretti, Giuseppina De Marco, Melissa De Servi, Luca Chiovato, Filomena Cetani, Paolo Vitti, Aldo Pinchera

Research output: Contribution to journalArticle

Abstract

Objective: TSH receptor (TSHr) mediates the activating action of TSH on the thyroid gland resulting in the growth and proliferation of thyrocytes and thyroid hormone production. TSHr is a major autoantigen in Graves' disease (GD) and is the target for TSHr antibodies. In GD, thyroid-stimulating anti-bodies (TSAb) are competitive agonists of TSH. In atrophic thyroiditis (AT), thyroid-stimulating blocking antibodies (TSHBAb) are TSH antagonists. The TSHr together with the LH receptor (LHr) and FSH receptor (FSHr) are G-protein-coupled receptors with considerable amino acid homologies in the extracellular domain. We studied the cross-reactivity of the antibodies measured in sera from patients with GD or AT on the LHr and FSHr function. Methods: We tested the activity of TSAb and TSHBAb in cell lines expressing the LHr and the FSHr. To this purpose a pSVL-FSHr construct was transfected in CHO cells and one clone was used. Results: Twenty-eight sera from patients with GD and four from patients with AT, known to contain TSHr antibodies measured with a radioreceptor assay, were selected. TSAb and TSHBAb activities were measured in CHO cells expressing the TSHr (CHO-TSHr). TSAb and TSHBAb were then tested with the cell lines expressing the LHr and the FSHr for their ability to elicit cAMP accumulation or inhibit FSH/LH-induced cAMP production. None of the TSAb identified was able to stimulate cAMP increase in CHO-LHr or CHO-FSHr. Similarly, none of the TSHBAb was able to block the cAMP response induced by FSH or LH in the respective cell lines. Conclusions: Our results confirm the notion of the organ-specific nature of the TSHr antibodies.

Original languageEnglish
Pages (from-to)381-387
Number of pages7
JournalEuropean Journal of Endocrinology
Volume150
Issue number3
DOIs
Publication statusPublished - Mar 2004

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Gonadotropin Receptors
FSH Receptors
LH Receptors
Eukaryotic Cells
Thyrotropin Receptors
Thyroid Gland
Thyroiditis
Graves Disease
CHO Cells
Cell Line
Thyroid-Stimulating Immunoglobulins
Radioligand Assay
Blocking Antibodies
G-Protein-Coupled Receptors
Serum
Thyroid Hormones
thyrotropin-binding inhibitory immunoglobulin
Clone Cells
Amino Acids
Antibodies

ASJC Scopus subject areas

  • Endocrinology

Cite this

Tonacchera, M., Ferrarini, E., Dimida, A., Agretti, P., De Marco, G., De Servi, M., ... Pinchera, A. (2004). TSH receptor antibodies do not alter the function of gonadotropin receptors stably expressed in eukaryotic cells. European Journal of Endocrinology, 150(3), 381-387. https://doi.org/10.1530/eje.0.1500381

TSH receptor antibodies do not alter the function of gonadotropin receptors stably expressed in eukaryotic cells. / Tonacchera, Massimo; Ferrarini, Eleonora; Dimida, Antonio; Agretti, Patrizia; De Marco, Giuseppina; De Servi, Melissa; Chiovato, Luca; Cetani, Filomena; Vitti, Paolo; Pinchera, Aldo.

In: European Journal of Endocrinology, Vol. 150, No. 3, 03.2004, p. 381-387.

Research output: Contribution to journalArticle

Tonacchera, M, Ferrarini, E, Dimida, A, Agretti, P, De Marco, G, De Servi, M, Chiovato, L, Cetani, F, Vitti, P & Pinchera, A 2004, 'TSH receptor antibodies do not alter the function of gonadotropin receptors stably expressed in eukaryotic cells', European Journal of Endocrinology, vol. 150, no. 3, pp. 381-387. https://doi.org/10.1530/eje.0.1500381
Tonacchera, Massimo ; Ferrarini, Eleonora ; Dimida, Antonio ; Agretti, Patrizia ; De Marco, Giuseppina ; De Servi, Melissa ; Chiovato, Luca ; Cetani, Filomena ; Vitti, Paolo ; Pinchera, Aldo. / TSH receptor antibodies do not alter the function of gonadotropin receptors stably expressed in eukaryotic cells. In: European Journal of Endocrinology. 2004 ; Vol. 150, No. 3. pp. 381-387.
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AU - Tonacchera, Massimo

AU - Ferrarini, Eleonora

AU - Dimida, Antonio

AU - Agretti, Patrizia

AU - De Marco, Giuseppina

AU - De Servi, Melissa

AU - Chiovato, Luca

AU - Cetani, Filomena

AU - Vitti, Paolo

AU - Pinchera, Aldo

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N2 - Objective: TSH receptor (TSHr) mediates the activating action of TSH on the thyroid gland resulting in the growth and proliferation of thyrocytes and thyroid hormone production. TSHr is a major autoantigen in Graves' disease (GD) and is the target for TSHr antibodies. In GD, thyroid-stimulating anti-bodies (TSAb) are competitive agonists of TSH. In atrophic thyroiditis (AT), thyroid-stimulating blocking antibodies (TSHBAb) are TSH antagonists. The TSHr together with the LH receptor (LHr) and FSH receptor (FSHr) are G-protein-coupled receptors with considerable amino acid homologies in the extracellular domain. We studied the cross-reactivity of the antibodies measured in sera from patients with GD or AT on the LHr and FSHr function. Methods: We tested the activity of TSAb and TSHBAb in cell lines expressing the LHr and the FSHr. To this purpose a pSVL-FSHr construct was transfected in CHO cells and one clone was used. Results: Twenty-eight sera from patients with GD and four from patients with AT, known to contain TSHr antibodies measured with a radioreceptor assay, were selected. TSAb and TSHBAb activities were measured in CHO cells expressing the TSHr (CHO-TSHr). TSAb and TSHBAb were then tested with the cell lines expressing the LHr and the FSHr for their ability to elicit cAMP accumulation or inhibit FSH/LH-induced cAMP production. None of the TSAb identified was able to stimulate cAMP increase in CHO-LHr or CHO-FSHr. Similarly, none of the TSHBAb was able to block the cAMP response induced by FSH or LH in the respective cell lines. Conclusions: Our results confirm the notion of the organ-specific nature of the TSHr antibodies.

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