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A molecular dissection of the glycoprotein hormone receptors

  • Conference paper
Insights into Receptor Function and New Drug Development Targets

Part of the book series: Research and Perspectives in Endocrine Interactions ((RPEI))

Summary

In glycoprotein hormone receptors, a subfamily of rhodopsin-like G protein-coupled receptors, the recognition and activation steps are carried out by separate domains of the proteins. Specificity of recognition of the hormones [thyrotropin (TSH), lutropin (LH), human chorionic gonadotropin (hCG), follitropin (FSH)] involves leucine-rich repeats (LRR) present in an aminoterminal ectodomain and can be associated with a limited number of residues at key positions of the LRRs. The mechanism by which binding of the hormones results in activation is proposed to involve switching of the ectodomain from a tethered inverse agonist to a full agonist of the serpentine, rhodopsin-like portion of the receptor. Unexpectedly, the picture is complicated by the observation that promiscuous activation of one of the receptors (FSHr) by hCG or TSH can result from activating mutations affecting the serpentine portion of the receptors.

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Authors and Affiliations

  1. IRIBHM, Université Libre de Bruxelles, B-1070, Brussels, Belgium

    Gilbert Vassart & Sabine Costagliola

  2. Service de Génétique Médicale, Hôpital Erasme, B-1070, Brussels, Belgium

    Gilbert Vassart

  3. Laboratori de Medicina Computacional, Unitat de Bioestadística, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193, Bellaterra, Spain

    Leonardo Pardo

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  1. Gilbert Vassart
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  2. Leonardo Pardo
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  3. Sabine Costagliola
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Editors and Affiliations

  1. Divisions of Neuroscience and Reproductive Biology, Departments of Physiology and Pharmacology and Cell and Developmental Biology, Oregon National Primate Research Center, Oregon Health and Science University, 505 NW 185th Avenue, Beaverton, Oregon, 97006, USA

    Michael Conn Ph.D.

  2. Institut Necker, 156, rue de Vaugirard, 75015, Paris, France

    Claude Kordon Ph.D.

  3. Pour la Recherche Thérapeutique, Fondation IPSEN, 24, rue Erlanger, 75781, Paris Cedex 16, France

    Yves Christen Ph.D.

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© 2006 Springer-Verlag Berlin Heidelberg

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Vassart, G., Pardo, L., Costagliola, S. (2006). A molecular dissection of the glycoprotein hormone receptors. In: Conn, M., Kordon, C., Christen, Y. (eds) Insights into Receptor Function and New Drug Development Targets. Research and Perspectives in Endocrine Interactions. Springer, Berlin, Heidelberg . https://doi.org/10.1007/3-540-34447-0_10

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