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Das GnRHR-Gen, seine Mutationen und deren Manifestation

The GnRHR gene, its mutations, and their phenotypic effects

  • Leitthema
  • Published:
Der Gynäkologe Aims and scope

Zusammenfassung

Der GnRH(Gonadotropin-releasing Hormon)-Rezeptor (GnRHR) ist ein zentraler Mediator der GnRH-Wirkung. Der Rezeptor ist als transmembranes Protein in der Zellmembran verankert. Durch extrazelluläre Bindung des Liganden an den extrazellulären Teil des Rezeptors wird dieser aktiviert und katalysiert als „G-protein-coupled receptor“ daraufhin intrazelluläre Vorgänge im Zusammenhang mit der GnRH-Wirkung. Kodiert wird der Rezeptor von einem auf dem humanen Chromosom 4 gelegenen Gen, dem GnRHR. Homozygote Mutationen des Gens sind über die kodierenden Teile der Exons des gesamten Gens verteilt beschrieben worden und können zu idiopathischem hypogonadotropem Hypogonadismus mit verspäteter oder ausbleibender Pubertätsentwicklung führen. Für einige Mutationen sind sog. Founder-Effekte beschrieben, und es werden Selektionsvorteile für Heterozygote durch beschleunigte Auslösung einer Stress-Amenorrhö diskutiert.

Abstract

The gonadotropin-releasing hormone (GnRH) receptor is an evolutionarily widespread central part of the GnRH network. As a member of the so-called G‑protein-coupled receptor family, the transmembrane protein becomes activated by engagement due to binding of its ligand. The receptor is encoded by GnRHR, a gene mapping to human chromosome 4. Homozygous mutations found to be spread over all coding parts of exons of GnRHR can lead to idiopathic hypogonadotropic hypogonadism with stalled or even primarily absent onset of puberty. Founder effects have been described for some of these mutations and advantages for their heterozygous carriers due to an earlier occurrence of stress-induced amenorrhea are under discussion.

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Danksagung und Entschuldigung

Wir danken Frau Dr. B. Rommel, Bremen, für die kritische Durchsicht und Kommentierung des Manuskriptes sowie Herrn Dr. C. Holzmann, Rostock, für kritische Durchsicht und Formatierung. Die Literatur zum GNRHR und seinen Mutationen ist sehr umfangreich. Wir waren für diesen Artikel gezwungen, daraus auszuwählen. Wenn ein Artikel nicht zitiert wurde, so beinhaltet das keine irgendwie geartete Wertung seiner Bedeutung im Vergleich zu den zitierten Artikeln.

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  1. Institut für Medizinische Genetik, Universitätsmedizin Rostock, Ernst-Heydemann-Straße 8, 18057, Rostock, Deutschland

    Jörn Bullerdiek

  2. Humangenetik, Universität Bremen, Bremen, Deutschland

    Jörn Bullerdiek

  3. Gynäkologische Endokrinologie und Reproduktionsmedizin, Frauenarztpraxis, Bremen, Deutschland

    Ute Bock-Steinweg

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  1. Jörn Bullerdiek
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Correspondence to Jörn Bullerdiek.

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R. Felberbaum, Kempten

W. Küpker, Baden-Baden

T. Strowitzki, Heidelberg

G. Emons, Göttingen

K. Diedrich, Lübeck

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Bullerdiek, J., Bock-Steinweg, U. Das GnRHR-Gen, seine Mutationen und deren Manifestation. Gynäkologe 53, 502–509 (2020). https://doi.org/10.1007/s00129-020-04631-1

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  • DOI: https://doi.org/10.1007/s00129-020-04631-1

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