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  • 1
    ISSN: 1573-6830
    Keywords: human gonadotropin-releasing hormone receptor ; baculovirus/insect cell ; Semliki Forest virus
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract 1. Two eukaryotic viral systems, the baculovirus/insect cell and the Semliki Forest virus systems, were tested for heterologous expression of human gonadotropin-releasing hormone receptor (GnRHR) cDNA. 2. An unmodified as well as a c-myc epitope-tagged human GnRH receptor was produced in two insect cell lines (Spodoptera frugiperda, Trichoplusia ni) after infection with the respective recombinant baculoviruses. In both insect cell lines, the receptor was identified by immunoblot analysis as a triplet of bands between 35 and 40 kDa. After deglycosylation of the receptor the molecular mass decreased to 35 kDa. The GnRH receptor was localized in membrane compartments within the infected insect cells. However, only in membranes of infected Trichoplusia ni insect cells could ≈2000 receptors per cell be detected. 3. Production of the GnRH receptor in BHK cells using the Semliki Forest virus system resulted in ≈50,000 receptors per cell. A maximal yield of 0.42 pmol/mg membrane protein was obtained 24 hr after electroporation of BHK cells with in vitro synthesized RNA. Binding of the antagonist [125I]Cetrorelix was saturable with a K D of 1.3 nM. The receptor produced in the BHK cells was further characterized by ligand displacement studies. The rank order of agonist and antagonist affinities was Cetrorelix 〉 Triptorelin 〉 Antide 〉 GnRH.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 0044-8249
    Keywords: Cytostatica ; Konformationsanalyse ; LHRH-Antagonisten ; Peptidmimetica ; Rezeptoren ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Hormone - und hier besonders die Geschlechtshormone - waren die ersten Wachstumsfaktoren, die als unfreiwillige Helfer des Krebses enttarnt wurden. Der Brustkrebs der Frau und das Prostatacarcinom des Mannes sind die bekanntesten der als hormonabhängig geltenden Tumore. Ein Blick in die Krebsstatistik zeigt, daß der Brustkrebs nach wie vor die häufigste Tumorerkrankung der Frau ist; beim Mann spielt im fortgeschrittenen Alter das Prostatacarcinom eine ähnlich dominierende Rolle. Die operative Ausschaltung der Hauptproduktionsstätten der Geschlechtshormone Östrogen und Testosteron durch Entfernung der Eierstöcke bzw. durch Kastration sind altbekannte und oft effektive, wenn auch wegen der psychischen Belastung durch solche Eingriffe problematische Therapien. Die moderne Hormontherapie beim fortgeschrittenen Brustkrebs und Prostatacarcinom versucht, dem Patienten solche unwiderruflichen operativen Eingriffe so lange wie möglich zu ersparen: durch Hormon-Antagonisten, z. B. LHRH-Antagonisten, die das eigentliche Hormon an der Entfaltung seiner wachstumsfördernden Wirkung hindern.
    Additional Material: 9 Ill.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 0570-0833
    Keywords: conformation analysis ; LHRH antagonists ; peptidomimetics ; receptors ; tumor therapy ; Antitumor agents ; Conformation analysis ; LHRH antagonists (luteinizing hormon-releasing hormon) ; Peptidomimetics ; Receptors ; Chemistry ; General Chemistry
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Chemistry and Pharmacology
    Notes: Hormones - and in particular, the sex hormones - were the first growth factors discovered to be involuntary helpers of cancer. Female breast cancer and male prostate cancer are the best known examples of tumors acknowledged to be hormone-dependent. A look at cancer statistics shows that breast cancer is still the most frequent cancer in women; in men, prostate cancer plays a similarly dominant role with increasing age. Shutting down the main production site of the sex hormones estrogen and testosterone either by removing the ovaries or by castration is a well-known and often effective therapy; however, these procedures can be problematic due to the concomittant psychological stress. Modern hormone therapy for advanced breast cancer and prostate cancer attempts to spare the patient such irreversible operative procedures for as long as possible, by using hormone antagonists, such as the LHRH antagonists, which hinder deployment of the hormone itself and thus its growth-promoting activity.
    Type of Medium: Electronic Resource
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