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Chemopreventive Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
The results of in vitro experiments have suggested that quercetin can inhibit the oxidation of other molecules, and so it is often classed as an antioxidant. This has some theoretical basis on the grounds that it has a polyphenolic structure that may stop oxidation by scavenging free radicals involved in oxidative chain reactions. Other results from in vitro experiments suggest that it has estrogenic activity through activation of both ERα and ERβ estrogen receptors with binding IC50 values of 1015 nM and 113 nM, respectively. Based on these figures, it would appear to be ERβ selective (by 9-fold), but approximately 2–3 orders of magnitude less potent than the endogenous hormone 17β-estradiol. It has also been reported that, in human breast tumor cell lines, quercetin can act as an agonist of the GPER (G Protein-Coupled Estrogen Receptor) and can activate or inhibit the activities of a range of other proteins. For example, it has also been reported to be a nonspecific protein kinase enzyme inhibitor. However, given that quercetin is metabolized so quickly after oral absorption, it is unlikely that any of these in vitro observations can be related to in vivo effects in humans.
Hormonal Regulation in the Treatment of Fibroids
Published in John C. Petrozza, Uterine Fibroids, 2020
Victoria Fitz, Steven L. Young
Estrogens signal primarily through two specific nuclear receptors, ER-alpha and ER-beta, though additional membrane-bound ER-alpha and the G-protein-coupled estrogen receptor (GPER) on the cell surface can also mediate estrogen responses. Estrogen is able to induce human fibroid cell proliferation in vitro [3] as well as fibroid growth in a rat model in vivo and in rat leiomyoma cells in vitro [4,5]. The production of estradiol by some leiomyomas [6] also suggests autocrine or intracrine pathways for estrogen to promote growth. Estrogen receptors alpha and beta are found in higher concentration in leiomyoma cells compared with surrounding normal myometrium. Estrogen activates fibroblasts within leiomyomas leading to proliferation and ECM deposition [7]. These and many other studies strongly implicate a role for estradiol in leiomyoma growth.
Roles of membrane and nuclear estrogen receptors in spermatogenesis
Published in C. Yan Cheng, Spermatogenesis, 2018
Paul S. Cooke, Manjunatha K. Nanjappa, Sergei G. Tevosian, Rex A. Hess
Expression of GPER in various testicular and other reproductive cell types, such as Sertoli cells, germ cells, epididymis, and sperm, is well documented. Consistent with this, estrogen actions mediated partially or entirely through GPER are known.22–26
Estrogen and estrogen receptors in kidney diseases
Published in Renal Failure, 2021
Hao-Yang Ma, Shuang Chen, Yang Du
The mechanisms of estrogen action are categorized into classical (genomic) and rapid (non-genomic) ones. In the classical pathway, estrogen binds to the ERs in the cytoplasm, leading to ER dimerization and translocation to the nucleus, where the estrogen–ER complex interacts with ERE sequences in target genes [16]. This process typically occurs within hours [65]. In recent decades, however, rapid or ‘non-genomic’ effects of estrogen (also termed non-nuclear or membrane initiated steroid signaling) has been reported [66]. This occurs through the ER located in or adjacent to the plasma membrane, or through other non-ER plasma membrane-associated estrogen-binding proteins, which usually takes seconds or minutes [67]. GPER has been identified as one of the main estrogen-sensitive receptors responsible for the rapid non-genomic action of estrogen [68]. The classical (genomic) and non-genomic estrogen signaling pathways are illustrated in Figure 1 [22,69].
Kaempferol-induced GPER upregulation attenuates atherosclerosis via the PI3K/AKT/Nrf2 pathway
Published in Pharmaceutical Biology, 2021
Zhuo Feng, Changyuan Wang, Yue Jin, Qiang Meng, Jingjing Wu, Huijun Sun
Compelling evidence confirmed that membrane G protein-coupled oestrogen receptor (GPER), a newly discovered ER activated by classic oestrogen and phytoestrogens, is associated with numerous diseases (Barton and Prossnitz 2015; Grande et al. 2020). In particular, the expression of GPER modulated by the regulator changed the concentration of oestrogen and further affected the deterioration of AS in postmenopausal women. In addition, GPER regulators stimulate the PI3K signal pathway to fight various diseases (Fan et al. 2018); this pathway is associated with the expression level of oestrogen (Pollard and Daniel 2019). Notably, PI3K/AKT/Nrf2 pathway is the most widely studied. However, whether kaempferol, as an activator of GPER, attenuates AS via modulation of the PI3K/AKT/Nrf2 signalling pathway is elusive.
G protein-coupled estrogen receptor 1 expression in normal myometrium, leiomyoma, and adenomyosis tissues of premenopausal women
Published in Gynecological Endocrinology, 2020
Mijin Kim, Yeon-Suk Kim, Jeong In Choi, Jun-Mo Kim, Hae-Hyeog Lee, Tae-Hee Kim
The non-nuclear estrogen receptor, GPR30, is encoded by the human GPER gene. In 2005, estradiol was found to be a high affinity ligand for GPR30. Based on this affinity, the receptor was renamed G protein binding estrogen receptor (GPER). GPER1, also known as GPR30, is characterized by rapid non-genomic signaling events. GPER is currently known to be expressed in numerous tissues, and research on its function is increasing substantially [8]. Estrogen binding to GPER1 results in calcium mobilization and phosphatidylinositol 3,4,5-trisphosphate synthesis and contributes to estrogen physiology and pathophysiology [9]. GPER1 expression was reported in MCF-7 and SKBr3 breast cancer [10], ovarian cancer [11], and endometriosis cell lines [12]. GPER1 expression has been shown to be related to endometrial and primary breast cancer [9,13,14]. GPER1 activation also stimulates endometrial cancer proliferation [15].