Estrogen Biosynthesis and Signal Transduction in Ovarian Disease

Xu, Xue-Ling; Huang, Zhengyuan; Yu, Kun; Li, Jun; Fu, Xiangwei; Deng, Shoulong

doi:10.3389/fendo.2022.827032

Cited by 20 publications

(14 citation statements)

References 163 publications

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“…It may also be indicated that ERα and ERβ regulate processes connected with the female reproductive system in regulating several other physiological and pathophysiological processes in the human body. Disrupted ER signaling leads to the development of different diseases, such as osteoporosis, neurodegeneration, inflammation and metabolic and cardiovascular diseases [ 19 ]; however, the most important indications to modify their activity connected with estrogen-related cancers such as breast [ 19 ], endometrial [ 20 ], cervical [ 21 ] and ovarian cancer [ 22 ].…”

Section: Resultsmentioning

confidence: 99%

Resveratrol Analogues as Selective Estrogen Signaling Pathway Modulators: Structure–Activity Relationship

et al. 2022

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Resveratrol is a plant-derived phytoalexin found in grapes, red wine and many other plants used in Asian folk medicine. It is extensively studied for pleiotropic biological activity. The most crucial are anticancer and chemopreventive properties. Resveratrol has also been reported to be an antioxidant and phytoestrogen. The phytoestrogenic activity of resveratrol was assayed in different in vitro and in vivo models. Although these works brought some, on the first look, conflicting results, it is commonly accepted that resveratrol interacts with estrogen receptors and functions as a mixed agonist/antagonist. It is widely accepted that the hydroxyl groups are crucial for resveratrol’s cytotoxic and antioxidative activity and are responsible for binding estrogen receptors. In this work, we assayed 11 resveratrol analogues, seven barring methoxy groups and six hydroxylated analogues in different combinations at positions 3, 4, 5 and 3′,4′,5′. For this purpose, recombined estrogen receptors and estrogen-dependent MCF-7 and Ishikawa cells were used. Our study was supported by in silico docking studies. We have shown that, resveratrol and 3,4,4′5′-tetrahydroxystilbene, 3,3′,4,5,5′-pentahydroxystilbene and 3,3′,4,4′,5,5′-hexahydroxystilbene may act as selective estrogen receptor modulators.

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Section: Resultsmentioning

confidence: 99%

Resveratrol Analogues as Selective Estrogen Signaling Pathway Modulators: Structure–Activity Relationship

et al. 2022

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“…In addition to tumor-intrinsic genetic factors, the tumor microenvironment is an emerging hallmark of cancer [75] and thus shapes EAOCs. One major player in the malignant transformation to EAOC is the estrogen concentration in the surrounding milieu, either exogenously provided by estrogen replacement therapy [76,77] or endogenously produced by the ovaries [78]. Hereby, high estrogen levels promote the proliferation of endometriotic cells via binding to the non-classical, G-protein-coupled estrogen receptor 1, followed by the activation of various signaling pathways such as the PI3K/AKT/mTOR [79], as reviewed by Kozieł et Piastowska-Ciesielska [80].…”

Section: Estrogen Concentrationmentioning

confidence: 99%

Endometriosis-Associated Ovarian Cancer: From Molecular Pathologies to Clinical Relevance

Steinbuch,

Lüß,

Eltrop

et al. 2024

IJMS

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Endometriosis is a chronic condition affecting reproductive-aged women, characterized by the growth of ectopic endometrial tissue. Despite being benign, endometriosis is associated with an increased risk of certain cancers, including endometriosis-associated ovarian cancer (EAOC). Ovarian cancer is rare, but more common in women with endometriosis, particularly endometrioid and clear-cell carcinomas. Factors such as hormonal imbalance, reproductive history, environmental exposures, and genetic predisposition contribute to the malignant transformation of endometriosis. Thus, understanding potential risk factors causing malignancy is crucial. Over the past few decades, various genetic mutations, microRNAs, as well as tumor microenvironmental factors have been identified, impacting pathways like PI3K/AKT/mTOR, DNA repair mechanisms, oxidative stress, and inflammation. Thus, this review aims to summarize molecular studies involved in EAOC pathogenesis as potential therapeutic targets. However, further research is needed to better understand the molecular and environmental factors driving EAOC development, to target the susceptibility of endometriotic lesions to malignant progression, and to identify effective therapeutic strategies.

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“…GPER is widely distributed in various tissues of the human body. GPER first attracted considerable attention in reproduction as an estrogen receptor that functioned in the breast [ 17 , 20 ], ovary [ 21 ], endometrium [ 22 , 23 ], testis [ 24 ], and prostate [ 25 , 26 ], as well as the placenta [ 27 , 28 ]. GPER is also found in other systems and organs, including the brain, lung, liver, heart, pancreatic islets, adipose tissue, vasculature, muscle, and skeleton, as well as in immune cells [ 29 , 30 ].…”

Section: Tissue Cellular Localization Ligands and Classical Signaling...mentioning

confidence: 99%

The Role of G Protein-Coupled Estrogen Receptor (GPER) in Vascular Pathology and Physiology

Xu,

Ma,

Wang

et al. 2023

Biomolecules

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Objective: Estrogen is indispensable in health and disease and mainly functions through its receptors. The protection of the cardiovascular system by estrogen and its receptors has been recognized for decades. Numerous studies with a focus on estrogen and its receptor system have been conducted to elucidate the underlying mechanism. Although nuclear estrogen receptors, including estrogen receptor-α and estrogen receptor-β, have been shown to be classical receptors that mediate genomic effects, studies now show that GPER mainly mediates rapid signaling events as well as transcriptional regulation via binding to estrogen as a membrane receptor. With the discovery of selective synthetic ligands for GPER and the utilization of GPER knockout mice, significant progress has been made in understanding the function of GPER. In this review, the tissue and cellular localizations, endogenous and exogenous ligands, and signaling pathways of GPER are systematically summarized in diverse physiological and diseased conditions. This article further emphasizes the role of GPER in vascular pathology and physiology, focusing on the latest research progress and evidence of GPER as a promising therapeutic target in hypertension, pulmonary hypertension, and atherosclerosis. Thus, selective regulation of GPER by its agonists and antagonists have the potential to be used in clinical practice for treating such diseases.

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Estrogen Biosynthesis and Signal Transduction in Ovarian Disease

Cited by 20 publications

References 163 publications

Resveratrol Analogues as Selective Estrogen Signaling Pathway Modulators: Structure–Activity Relationship

Resveratrol Analogues as Selective Estrogen Signaling Pathway Modulators: Structure–Activity Relationship

Endometriosis-Associated Ovarian Cancer: From Molecular Pathologies to Clinical Relevance

The Role of G Protein-Coupled Estrogen Receptor (GPER) in Vascular Pathology and Physiology

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