Molecular mechanism of estrogen–estrogen receptor signaling

Yaşar, Pelin; Ayaz, Gamze; User, Sırma Damla; Güpür, Gizem; Muyan, Mesut

doi:10.1002/rmb2.12006

Cited by 322 publications

(254 citation statements)

References 214 publications

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“…This moderately explains why differences in ERE sequences, such as those resulting from inter-individual gene variability or mutations, can affect the activation of gene expression (Loven, Wood, & Nardulli, 2001; Yi et al, 2002). In addition, specific ERE sequences can cause allosteric changes in the receptor’s structure, and thus alter the ability of the complex to recruit coactivators and transcription factors that may contribute to ER biological activity (Hall, McDonnell, & Korach, 2002; Yaşar, Ayaz, User, Güpür, & Muyan, 2017). …”

Section: Nuclear Estrogen Receptors: Direct Genomic Signalingmentioning

confidence: 99%

Estrogen receptor signaling mechanisms

Fuentes

Silveyra

2019

Advances in Protein Chemistry and Structural Biology

542

461

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The primary female sex hormones, estrogens, are responsible for the control of functions of the female reproductive system, as well as the development of secondary sexual characteristics that appear during puberty and sexual maturity. Estrogens exert their actions by binding to specific receptors, the estrogen receptors (ERs), which in turn activate transcriptional processes and/or signaling events that result in the control of gene expression. These actions can be mediated by direct binding of estrogen receptor complexes to specific sequences in gene promoters (genomic effects), or by mechanisms that do not involve direct binding to DNA (non-genomic effects). Whether acting via direct nuclear effects, indirect non-nuclear actions, or a combination of both, the effects of estrogens on gene expression are controlled by highly regulated complex mechanisms. In this chapter, we summarize the knowledge gained in the past 60 years since the discovery of the estrogen receptors on the mechanisms governing estrogen-mediated gene expression. We provide an overview of estrogen biosynthesis, and we describe the main mechanisms by which the female sex hormone controls gene transcription in different tissues and cell types. Specifically, we address the molecular events governing regulation of gene expression via the nuclear estrogen receptors (ERα, and ERβ) and the membrane estrogen receptor (GPER1). We also describe mechanisms of cross-talk between signaling cascades activated by both nuclear and membrane estrogen receptors. Finally, we discuss natural compounds that are able to target specific estrogen receptors and their implications for human health and medical therapeutics.

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Section: Nuclear Estrogen Receptors: Direct Genomic Signalingmentioning

confidence: 99%

Estrogen receptor signaling mechanisms

Fuentes

Silveyra

2019

Advances in Protein Chemistry and Structural Biology

542

461

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“…Although previous studies did not find an association between rs4870044 and muscle strength [64][65][66] , we suggest that the discrepancy between those studies and our study might be attributable to us defining sarcopenia by the %SMM while the other studies assessed the relationship with muscle strength. Whatever the cause of the discrepancy, the higher risk of sarcopenia in T-allele carriers may be related to the physiological activities of oestrogen, mediated by oestrogen receptors 67,68 where lower levels of oestrogen have previously been associated with low bone mass and bone mineral density 69,70 , as well as low muscle mass 71 and muscle strength 71,72 .…”

Section: Sarcopeniamentioning

confidence: 99%

Prevalence and association of single nucleotide polymorphisms with sarcopenia in older women depends on definition

Khanal

Stebbings

et al. 2020

Sci Rep

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The prevalence of sarcopenia depends on the definition used. There are, however, consistent sarcopenic characteristics, including a low muscle mass and muscle strength. Few studies have investigated the relationship between sarcopenia and genotype. A cross-sectional study was conducted with 307 community-dwelling ≥60-year-old women in South Cheshire, UK. Handgrip strength was assessed with a handgrip dynamometer and skeletal muscle mass was estimated using bioelectrical impedance. DNA was extracted from saliva (∼38%) or blood (∼62%) and 24 single-nucleotide polymorphisms (SNPs) were genotyped. Three established sarcopenia definitions -%Skeletal Muscle Mass (%SMM), Skeletal Muscle Mass Index (SMI) and European Working Group on Sarcopenia in Older People (EWGSOP) -were used to assess sarcopenia prevalence. Binary logistic regression with age as covariate was used to identify SNPs associated with sarcopenia. The prevalence of sarcopenia was: %SMM 14.7%, SMI 60.6% and EWGSOP 1.3%. Four SNPs were associated with the %SMM and SMI definitions of sarcopenia; FTO rs9939609, ESR1 rs4870044, NOS3 rs1799983 and TRHR rs7832552. The first three were associated with the %SMM definition, and TRHR rs7832552 with the SMI definition, but none were common to both sarcopenia definitions. The gene variants associated with sarcopenia may help proper counselling and interventions to prevent individuals from developing sarcopenia.Sarcopenia is defined as an ageing-related loss of both muscle mass and strength below a threshold level 1 . It is an important predictor of adverse outcomes such as limited mobility, increased risk of falls, decreased quality of life (QoL), hospitalization and mortality, and contributes to tens of millions of pounds of health care costs in the UK 1-3 . Although muscle weakness and skeletal muscle atrophy are overt characteristics of this geriatric syndrome, there is ongoing debate on the operational definition, screening and diagnosis, and optimal management and treatment of the condition 1,4-6 . The considerable heterogeneity in the reported prevalence of sarcopenia is largely attributable to the different definitions or cut-offs used 7-9 .The fact that some elderly do not show sarcopenia, whilst others of the same age do 10,11 , suggests that some individuals are more susceptible to sarcopenia than others. The different susceptibility is likely due to a combination of factors including physical activity, diet, sedentary behaviour and genetics [12][13][14][15] . Several studies have reported an association of single nucleotide polymorphisms (SNPs) with lean mass, muscle volume and muscle strength [16][17][18] . It is thus possible that individuals carrying favourable gene variants are less susceptible to sarcopenia and hence can maintain independence until later life. To date, five studies have investigated the association of SNPs with sarcopenia; limited to VDR, IL6, ACTN3 and MSTN polymorphisms [19][20][21][22][23] . The studies identified an association of ACTN3 and VDR gene variants with sarcopenia, but di...

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“…In mammary glands, ERα is expressed mainly in mammary epithelial cells. Although there are various functional models of ERα action, in the classical mechanism of ERα, estrogen-bound ERα forms a dimer, localizes in the nucleus, and binds to its DNA binding site to regulate gene expression (reviews, (12,15,(19)(20)(21)). Thus far, various ERα-regulated genes have been identified (13,14,16); these include growth regulating estrogen receptor binding 1 (GREB1), trefoil factor 1 (TFF1, pS2) (22,23).…”

Section: Introductionmentioning

confidence: 99%

Estrogen induces mammary ductal dysplasia

Itou

Takahashi

Sasanuma

et al. 2019

Preprint

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Mammary ductal dysplasia is a phenotype observed in precancerous lesions and earlystage breast cancer. However, the mechanism of dysplasia formation remains elusive.Here we show, by establishing a novel dysplasia model system, that estrogen, a female hormone, has the potential to cause mammary ductal dysplasia. We injected estradiol (E2), the most active form of estrogen, daily into scid mice with a defect in nonhomologous end joining repair and observed dysplasia formation with cell proliferation at day 30.Moreover, we found that isoflavones inhibited E2-induced dysplasia formation. Our dysplasia model system provides insight into the mechanistic understanding of breast tumorigenesis, and the development of breast cancer prevention.

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Molecular mechanism of estrogen–estrogen receptor signaling

Cited by 322 publications

References 214 publications

Estrogen receptor signaling mechanisms

Estrogen receptor signaling mechanisms

Prevalence and association of single nucleotide polymorphisms with sarcopenia in older women depends on definition

Estrogen induces mammary ductal dysplasia

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