The estrogen metabolites 2-methoxyestradiol and 2-hydroxyestradiol inhibit endometriotic cell proliferation in estrogen-receptor-independent manner

Samartzis EP, Eleftherios Pierre Samartzis, Eleftherios P Samartzis, Patrick Imesch, Imesch P, Twiehaus A, Anja Twiehaus, Raghvendra K. Dubey, Brigitte Leeners
Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology · 2016 · vol. 32(7) , pp. 529–533 · doi:10.3109/09513590.2015.1137094 · PMID:26800447 · W2290229020
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Estrogen metabolites 2-methoxyestradiol and 2-hydroxyestradiol inhibited endometriotic cell proliferation in pharmacological doses through partially estrogen-receptor-independent mechanisms.

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Abstract

Endometriosis, a painful disorder associated with infertility, is estimated to occur in approximately 7-10% of reproductive age women. Although endometriosis is considered as an estrogen-dependent disease, the role of estrogen metabolites via receptor-independent mechanisms has not yet been comprehensively clarified. In the present study, growth studies were performed comparing the effect of estradiol (E2), estrogen metabolites, that is, 2-hydroxyestradiol (2-OHE2) and 2-methoxyestradiol (2-ME), as well as estrogen-receptor-independent mechanisms using the estrogen receptor antagonist fulvestrant, on cell proliferation of endometriotic cells. The estrogen metabolites 2-OHE2 and 2-ME inhibited cell growth in a dose-dependent manner in pharmacological doses. Lower concentrations of 2-OHE2 had a stimulating effect on cell proliferation while pharmacologic doses exerted an antimitogenic effect. The effects on cell growth were at least partially receptor-independent, as demonstrated by simultaneous receptor antagonization with fulvestrant. In conclusion, our results demonstrate that in pharmacological doses the estrogen metabolites 2-ME and 2-OHE2 show inhibiting effects on the proliferation of endometriotic cells and may be promising substances for the treatment of endometriosis.
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Condition tags

endometriosisinfertility

MeSH descriptors

Cell Proliferation Endometriosis Estradiol Estrogen Receptor Antagonists 2-Methoxyestradiol 2-Methoxyestradiol Cell Line Cell Line Cell Proliferation Cell Proliferation Dose-Response Relationship, Drug Dose-Response Relationship, Drug Endometriosis Endometriosis Estradiol Estradiol Estradiol Estrogen Receptor Antagonists Estrogen Receptor Antagonists Female

Citation neighborhood

Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. [ expand to 2 hops ] — adds papers reached through this work's immediate citers/citees. Heavier; up to 60 extra dots.

References (36)

Cited by (4)

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