Östrogenabhängige Neoplasien - welche Bedeutung haben Estradiolmetaboliten

Zusammenfassung

Estradiol kann zu Abbauprodukten metabolisiert werden, die selbst in sehr geringen Konzentrationen noch verschiedene, teils gegensätzliche Wirkungen entfalten, wie in eigenen Untersuchungen z. B. hinsichtlich (anti)angiogenetischer Wirkungen nachgewiesen. Spezifisch antikanzerogene Wirkungen werden dem 2-Hydroxyestron und vor allem 2-Methoxyestradiol zugeschrieben. Demgegenüber können 16α-Hydroxyestron und 4-Hydroxyöstrogene unter bestimmten Bedingungen genotoxische Eigenschaften entfalten. Ferner wird bei einigen Krebsarten eine erhöhte Produktion von wachstumsstimulierenden Estradiolmetaboliten beobachtet. Hier wurde speziell das Verhältnis 2-Hydroxyestron zu 16α-Hydroxyestron untersucht, das vor allem bei postmenopausalen Brustkrebspatientinnen in klinischen, auch eigenen Studien sich bei Bestimmung aus dem Urin verringert zeigte. Derzeit wird untersucht, inwieweit durch Metabolitenbestimmungen auch aus dem Blut oder direkt im Brustgewebe mittels neuer hochsensitiver Labortechniken prädiktive Aussagen möglich sind. Dabei ist allerdings zu berücksichtigen, dass der Estradiolabbau durch externe Faktoren wie Ernährung, Rauchen, Sport und Medikamente wie L-Thyroxin und H2-Blocker beeinflusst werden kann. Wir konnten nachweisen, dass die Metabolitenproduktion bei Behandlung mit Estradiol von der Applikationsform abhängt und durch Zusatz von verschiedenen Gestagenen unterschiedlich beeinflusst werden kann. Inwieweit die Untersuchung von Genpolymorphismen für Enzyme, die am Estradiolabbau beteiligt sind, zur Feststellung bzw. Behandlung von Risikopatientinnen hilfreich sein kann, bedarf unseres Erachtens noch weiterer Forschungsanstrengungen.

Abstract

Estradiol can be metabolized to substances eliciting different, partly opposite effects even at low concentrations as shown in own investigations, e. g., regarding (anti)angiogenic actions. Specific anticancerogenic effects are ascribed to 2-hydroxyestrone and particularly 2-methoxyestradiol. In contrast, 16α-hydroxyestrone and the 4-hydroxyestrogens may be genotoxic under certain circumstances. Furthermore there are indications that endogenous production of proliferation-stimulating metabolites is raised in some cancers. Especially the urinary excretion of 2-hydroxyestrone to 16α-hydroxyestrone was investigated showing in own and other clinical studies a lower ratio in postmenopausal women with breast cancer. Research is ongoing inasfar the determination of estradiol metabolites also in blood or directly in the breast tissue by means of sensitive laboratory methods may allow predictive statements. However, it has be to consider that estradiol metabolism can be influenced by external factors such as nutrition, smoking, sports and drugs such as L-thyroxine and H2-antagonists. We were able to demonstrate that estradiol metabolism during estradiol treatment depends on the application mode and might be differently influenced by addition of the various progestins. Whether the investigation of gene polymorphism of enzymes, which are involved in estradiol metabolism, may be helpful for the assessment or treatment of risk patients, to our opinion needs further research.

Schlüsselwörter

Estradiolmetabolite - Neoplasien

Key words

Estradiol metabolites - neoplasia

Literatur

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