Asialoagalacto-Choriongonadotropin, an Antagonist of the Action of Graves' Immunoglobulins in Human Thyroid Membranes with a Limited Affinity for Hepatic Receptors

Hoermann, Rudolf; Rehbach, K; Mann, Klaus

doi:10.1055/s-2007-1004883

Cited by 2 publications

(1 citation statement)

References 3 publications

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“…The aspects ofthe physiology ofasialoagalacto-hCG related to its interaction with the thyroid TSH receptor have apparently not been examined previously, except for some preliminary results published by our group (34). Only, some data on the interaction of this hCG variant with the ovarian and testis hCG receptor, mainly ofrat origin, are available (35)(36)(37)(38).…”

Section: Discussionmentioning

confidence: 99%

Asialoagalacto-human chorionic gonadotropin, a carbohydrate-modified variant of human chorionic gonadotropin, antagonizes the stimulatory actions of bovine thyroid-stimulating hormone on thyroid function and HLA-DR expression in human thyroid in vitro and in vivo.

Hoermann¹,

Schumm-Draeger²,

Rehbach³

et al. 1991

J. Clin. Invest.

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The concept of using thyroid-stimulating hormone (TSH) receptor antagonists in the management of Graves' disease is intriguing. Therefore, we investigated a TSH receptor antagonist derived from human chorionic gonadotropin (hCG) with respect to TSH receptor binding, adenylate cyclase activity, thyroid hormone release, and HLA class II antigen expression in vitro and in an in vivo model.A variant of hCG, asialoagalacto-hCG, like asialo-hCG and unlike hCG itself, inhibited both '25I-bTSH binding and cAMP response to bTSH in human thyroid membranes. However, like intact or deglycosylated hCG and unlike asialo-hCG, asialoagalacto-hCG displayed a limited affinity for hepatic asialoglycoprotein receptors, a likely marker for its in vivo turnover rate. It proved capable of inhibiting bTSH-stimulated thyroid hormone release in human thyroid slices as well as in the nude mouse bearing human thyroid transplants. It also prevented bTSH induced hypertrophy of transplanted thyrocytes. Further, HLA-DR expression induced by bTSH in the presence of y-interferon on human thyrocytes was inhibited.In conclusion, we present evidence that asialoagalacto-hCG antagonizes bTSH actions on thyroid function and HLA-DR expression in human thyroid in vitro and, more importantly, in an in vivo model. Hence, the hCG variant described here or similar agents should warrant further exploration in the study and treatment of Graves' disease. (J. Clin. Invest. 1991.

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Section: Discussionmentioning

confidence: 99%

Asialoagalacto-human chorionic gonadotropin, a carbohydrate-modified variant of human chorionic gonadotropin, antagonizes the stimulatory actions of bovine thyroid-stimulating hormone on thyroid function and HLA-DR expression in human thyroid in vitro and in vivo.

Hoermann¹,

Schumm-Draeger²,

Rehbach³

et al. 1991

J. Clin. Invest.

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Inhibition of Functional and Immunological Responses to Thyroid-Stimulating Antibodies from Patients with Graves' Disease by Blockade of the Thyrotropin Receptor

Hoermann¹,

Schumm–Draeger²,

Mann³

1993

Thyroid

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Thyrotropin (TSH) receptor is the main autoantigen and the target of thyroid-stimulating antibodies in Graves' disease. In the present studies, in order to shed further light on the role of TSH receptor in thyroid autoimmune disease, we investigated the effects of TSH receptor blockade on functional and immunological responses to thyroid stimulation by Graves' immunoglobulins in the nude mouse bearing human thyroid transplants. Injecting the nude mice with purified Graves' immunoglobulins G resulted in a dose-dependent stimulation of thyroid hormone production, an inducement of cellular hypertrophy of transplant thyrocytes, and an expression of the HLA-DR antigen by up to 75% of the transplant thyroid follicular cells. Treatment of the animals with the TSH receptor antagonist asialoagalacto-hCG was able to inhibit the stimulation by Graves' immunoglobulins G of thyroxine production, cellular hypertrophy of transplant thyrocytes, and HLA-DR expression by thyroid follicular cells in the human transplants. The present data provide direct evidence for an involvement of the human TSH receptor in mediating both the functional disturbance (hyperthyroidism) and the immunological disorder in Graves' disease and add further support to the concept of using TSH receptor antagonists in the management of the disease.

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Asialoagalacto-Choriongonadotropin, an Antagonist of the Action of Graves' Immunoglobulins in Human Thyroid Membranes with a Limited Affinity for Hepatic Receptors

Cited by 2 publications

References 3 publications

Asialoagalacto-human chorionic gonadotropin, a carbohydrate-modified variant of human chorionic gonadotropin, antagonizes the stimulatory actions of bovine thyroid-stimulating hormone on thyroid function and HLA-DR expression in human thyroid in vitro and in vivo.

Asialoagalacto-human chorionic gonadotropin, a carbohydrate-modified variant of human chorionic gonadotropin, antagonizes the stimulatory actions of bovine thyroid-stimulating hormone on thyroid function and HLA-DR expression in human thyroid in vitro and in vivo.

Inhibition of Functional and Immunological Responses to Thyroid-Stimulating Antibodies from Patients with Graves' Disease by Blockade of the Thyrotropin Receptor

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