Aromatase und Cyclooxygenase-2 – neue Ansätze in der Endometriosetherapie?

Andreas D. Ebert, Anna Starzinski‐Powitz
In: Der Gynäkologe · 2002 · vol. 35(3) , pp. 250–254 · doi:10.1007/s00129-002-1159-7 · W1972233009
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Aromatase overexpression and COX-2 upregulation in endometriosis increase local estradiol and prostaglandin E2, promoting proliferation and invasiveness, suggesting these as new therapeutic targets.

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The paper reviews molecular findings in endometriosis and positions aromatase (p450arom) and cyclooxygenase-2 (COX-2) as potential therapeutic targets. It describes aromatase overexpression in endometriotic tissue, which increases local estrogen biosynthesis and thereby upregulates COX-2 and prostaglandin E2 production, and it also notes deficient 17β-hydroxysteroid dehydrogenase type 2 expression that reduces conversion of estradiol to estrone; together these changes promote higher local estradiol and prostaglandin E2 levels, which in various human cell lines are associated with proliferation, migration, angiogenesis, resistance to apoptosis, and invasiveness. The main limitation is that the work is a narrative review emphasizing mechanistic and cell-line associations rather than presenting new clinical outcome data or controlled trials. This paper is centrally about endometriosis — it argues for aromatase- and COX-2–focused endometriosis therapy based on described molecular aberrations and downstream effects.

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Zusammenfassung Bei der medikamentösen Behandlung der Endometriose zielen bisher alle modernen Therapiestrategien auf die ovarielle Downregulation oder die Antagonisierung der Östrogeneffekte am Endometrioseherd. Kürzlich wurde die Überexpression der Aromatase in Endometriosegewebe entdeckt. Die Aromatase (p450arom) ist für die Konversion der C19-Androgene zu Östrogen in menschlichem Gewebe verantwortlich. Die Aromataseüberexpression hat eine verstärkte lokale Östrogenbiosynthese zur Folge, die über die Hochregulation der Cyclooxygenase-2 (COX-2) eine Stimulation der Prostaglandin E2-Produktion bewirkt. Außerdem ist im Endometriosegewebe die Expression von 17β-Hydroxysteroiddehydrogenase Typ 2 defizitär, was die lokale Umwandlung von Östradiol in Östron erschwert. Diese beiden molekularen Aberationen führen zu einer gesteigerten lokalen Konzentration von Östradiol und Prostaglandin E2. In verschiedenen menschlichen Zelllinien sind diese Veränderungen mit Zellproliferation, Migration, Angiogenese, Apoptoseresistenz und Invasivität assoziiert. Daher werden Aromatase und COX-2 als neue, vielversprechende therapeutische Targets angesehen. Abstract Therapeutic management of endometriosis-associated pain or recurrent disease is primarily aimed at downregulating the ovarian function or at antagonizing the effect of estrogen in ectopic endometrial implants. Recently, aromatase overexpression has been detected in endometriotic tissue. Aromatase (p450arom) is responsible for conversion of C19 androgens to estrogen in several human tissues. Aromatase activity gives rise to local estrogen biosynthesis, which stimulates prostaglandin E2 production by upregulation of cyclooxygenase-2 (COX-2). Another abnormality in endometriosis, i. e. the deficiency in 17β-hydroxysteroiddehydrogenase type 2 (17β-HSD Type 2) expression, impairs the inactivation of estradiol to estrone. These molecular aberrations favour the accumulation of local estradiol and prostaglandin E2 in endometriosis. In several human cell lines, elevated prostaglandin and estrogen concentrations are associated with proliferation, migration, angiogenesis, apoptosis resistance, and invasiveness. Consequentely, aromatase and COX-2 might be promising new therapeutic targets. Similar content being viewed by others Author information Authors and Affiliations Rights and permissions About this article Cite this article Ebert, A., Starzinski-Powitz, A. Aromatase und Cyclooxygenase-2 – neue Ansätze in der Endometriosetherapie?. Gynäkologe 35, 250–254 (2002). https://doi.org/10.1007/s00129-002-1159-7 Published: Issue date: DOI: https://doi.org/10.1007/s00129-002-1159-7

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