Comparative study of estrogen receptor α, β mRNA expressions of endometriosis and normal endometrium in women and analysis of potential synthetic anti-estrogens in silico

In: Journal of Biological Research - Bollettino della Società Italiana di Biologia Sperimentale · 2018 · vol. 91(2) · doi:10.4081/jbr.2018.7550 · W2902290990
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This study found higher ERβ mRNA expression in endometriosis compared to normal endometrium and identified Ral2 and Aco1 as potential inhibitors for ERα and ERβ respectively.

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This study compared estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ) mRNA expression in women with endometriosis versus normal endometrium controls (n=18), using quantitative real-time PCR, and measured serum estradiol levels in endometriosis patients during the menstrual proliferation phase via ELISA. ERβ mRNA was significantly higher in the endometriosis group than in controls (P<0.05), while estradiol did not correlate with ERα expression and showed only a weak correlation with ERβ mRNA. In silico molecular docking indicated different binding interactions of ERα and ERβ with synthetic antiestrogens, with Ral2 best inhibiting ERα and Aco1 best inhibiting ERβ, while the paper provides no direct in vitro or in vivo validation. This paper is centrally about endometriosis — it specifically measures ERα/ERβ mRNA expression in endometriosis tissue compared with normal endometrium and links ERβ upregulation and docking-identified antiestrogen targets to endometriosis-related biology.

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Abstract

Endometriosis is a multifactorial disease in which genetic and environmental factors interact causing its pathogenesis. The aim of this study was to investigate the expression pattern of estrogen receptor α (ERα) and β (ERβ) in endometriosis patients compared to normal endometrioum (n=18) as a control by using Quantitative Real Time PCR method. Moreover, we also measured serum estradiol levels of endometriosis patients in the proliferation phase of the menstrual cycle using the enzyme-linked immunosorbent assay method. The mRNA expression of ERβ was significantly higher in the endometriosis group compared to control, and the result of t-test showed that were significantly different (P<0.05). Overexpression of ERβ in endometriosis was likely to have other significant important impacts in the pathology of endometriosis that allowed ERβ to stimulate prostaglandin production in endometriosis tissue and cells. Estradiol content did not correlate with the ERα expression, and it is weakly correlated with ERβ mRNA expression. Molecular docking analysis showed that ERα and ERβ have different binding interactions with synthetic antiestrogens, whereas the best inhibitor was Ral2 to ERα and Aco1 to ERβ. Thus, both inhibitors could be used as leads in further investigation of ERα, ERβ inhibitory activities in vitro and in vivo.
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Comparative study of estrogen receptor α, β mRNA expressions of endometriosis and normal endometrium in women and analysis of potential synthetic anti-estrogens in silico All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher. Published: 28 November 2018 Endometriosis is a multifactorial disease in which genetic and environmental factors interact causing its pathogenesis. The aim of this study was to investigate the expression pattern of estrogen receptor α (ERα) and β (ERβ) in endometriosis patients compared to normal endometrioum (n=18) as a control by using Quantitative Real Time PCR method. Moreover, we also measured serum estradiol levels of endometriosis patients in the proliferation phase of the menstrual cycle using the enzyme-linked immunosorbent assay method. The mRNA expression of ERβ was significantly higher in the endometriosis group compared to control, and the result of t-test showed that were significantly different (P<0.05). Overexpression of ERβ in endometriosis was likely to have other significant important impacts in the pathology of endometriosis that allowed ERβ to stimulate prostaglandin production in endometriosis tissue and cells. Estradiol content did not correlate with the ERα expression, and it is weakly correlated with ERβ mRNA expression. Molecular docking analysis showed that ERα and ERβ have different binding interactions with synthetic antiestrogens, whereas the best inhibitor was Ral2 to ERα and Aco1 to ERβ. Thus, both inhibitors could be used as leads in further investigation of ERα, ERβ inhibitory activities in vitro and in vivo. 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