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Thyrotropic action of human chorionic gonadotropin

M Yoshimura1, J M Hershman

  • 1Second Department of Internal Medicine, Kansai Medical University, Osaka, Japan.

Thyroid : Official Journal of the American Thyroid Association
|October 1, 1995
PubMed
Summary

Human chorionic gonadotropin (hCG) has thyrotropic activity, stimulating the thyroid. Modifications like deglycosylation and the absence of the beta-CTP enhance hCG

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Area of Science:

  • Endocrinology
  • Reproductive Biology
  • Molecular Endocrinology

Background:

  • Hyperthyroidism is observed in patients with trophoblastic tumors, linked to elevated human chorionic gonadotropin (hCG) and suppressed TSH.
  • Structural homology between hCG, thyroid-stimulating hormone (TSH), and their receptors explains hCG's thyrotropic activity.
  • The thyrotropic action of hCG is clinically significant in normal pregnancy and hyperemesis gravidarum.

Purpose of the Study:

  • To investigate the structural basis and clinical implications of hCG's thyrotropic activity.
  • To understand how hCG modifications influence its potency at the TSH receptor.
  • To elucidate the role of hCG in gestational thyrotoxicosis and trophoblastic disease-associated hyperthyroidism.

Main Methods:

  • Comparison of purified human luteinizing hormone (hLH) and hCG binding to recombinant human TSH receptor.
  • Assessment of a recombinant mutant hCG lacking the beta-CTP's thyrotropic potency.
  • Analysis of nicked, deglycosylated, and desialylated hCG preparations' activity on recombinant TSH receptors.

Main Results:

  • Human LH is more potent than hCG at the TSH receptor; the hCG beta-CTP may prevent overt hyperthyroidism in pregnancy.
  • Nicked, deglycosylated, and desialylated hCG variants exhibit significantly enhanced thyrotropic potency.
  • Basic hCG isoforms and beta-CTP truncated hCG show higher bioactivity/immunoactivity ratios, correlating with lower sialic acid content.

Conclusions:

  • The thyrotropic activity of hCG is influenced by its molecular structure, metabolism, and glycosylation state.
  • Modifications like deglycosylation and truncation of the beta-CTP increase hCG's thyrotropic potency.
  • Understanding hCG's interaction with the TSH receptor is crucial for explaining gestational thyrotoxicosis and trophoblastic disease-related hyperthyroidism.

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