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.

Abstract

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.

Inhibitory Effect of Thyroid Blocking Antibody (TBAb) on the Thyroid Stimulatory Effect of Human Chorionic Gonadotropin (HCG ) and Equine Chorionic Gonadotropin (ECG)

“…deglycosylated-HCG (asialo-or asialoagalacto-HCG) is a competitive antagonist of TSH binding to TSHR. Because of increased TSHR binding compared to HCG, it has blocking action on cAMP production by TSH and TSAb [6][7][8][9][10][11]. in the present experiment we examined the inhibitory effect of TBAb on the thyroid stimulating activity of HCG and ECG.…”

“…There are many reports that HCG has the thyroid hormone releasing activity via TSHR binding [3][4][5][6][7][8][9][10][11]. Furthermore, the thyroid stimulating activity of HCG is blocked by TBAb [11].…”

“…deglycosylated HCG (asialo-or asialoagalacto-HCG) is a competitive antagonist of TSH because of increased TSHR binding compared to HCG. An inhibitory effect of asialo-HCG or asialoagalacto-HCG on the thyroid stimulating activity of TSAb has been reported [6][7][8][9][10]. These facts suggest that TSH, TSAb, HCG and deglycosylated-HCG may bind to a similar region of TSH R. in the present study we examined the effects of TBAb on the thyroid stimulating activity of HCG and equine chorionic gonadotropin (ECG).…”

“…Inhibitory Effect of Thyroid Blocking Antibody (TBAb) on the Thyroid Stimulatory Effect of Human Chorionic Gonadotropin (HCG) and Equine Chorionic Gonadotropin (ECG) YukiO OCHi 1) , MASAnARi HAMAZu 2) , YOSHiHiRO kAJiTA 3) , TAkASHi HACHiYA 4) And MASARu HAMAOki 5) roid stimulating activity through binding to the TSHR [3][4][5][6][7][8][9][10][11]. deglycosylated HCG (asialo-or asialoagalacto-HCG) is a competitive antagonist of TSH because of increased TSHR binding compared to HCG.…”

Molecular heterogeneity of human chorionic gonadotropin in serum and urine from patients with trophoblastic tumors

“…Particularly the more acidic variants of hCG that are present mainly in tumor samples have been shown to exhibit a prolonged plasma half-life compared to the hCG standard preparation [6]. Also, certain variants of hCG are capable of strongly interacting with other glycoprotein hormone receptors, particularly thyroid-stimulating hormone receptor, functioning either as agonists or antagonists at this receptor [16,25]. Whenever possible, future studies should therefore, instead of relying on urinary materials, directly assess the biological activities of hCG forms that are present in the circulation.…”