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Estrogen insensitivity syndrome (EIS) is a rare genetic disorder characterized by an autosomal dominant inheritance pattern. The disease results from a pathogenic variant in the ESR1 (estrogen receptor 1) gene, leading to estrogen resistance in individuals possessing the 46, XX karyotype. The alpha receptor, which is predominant in peripheral tissues, is responsible for estrogen action. As a result, pathogenic variants in the ESR1 gene can cause various disorders, such as changes in secondary sexual characteristics, increased concentrations of estrogen and gonadotropins, and delayed bone maturation. Here, the case of a 13-year-old girl, with high estrogen and gonadotropin concentrations, lack of breast development, uterine growth and delayed bone age is described. The patient's parents were related. She was found to have a homozygous pathogenic variant in the ESR1 gene located on chromosome 6q25, which interferes with estrogen signaling. This case supports that disruption of ESR1 causes profound estrogen resistance in females. [ABSTRACT FROM AUTHOR]

The nursing ability of productive ewes has been a subject of extensive research. From today's perspective, the survivability of multiple lambs of highly productive ewes in birth time depends largely on the number of functional teats. Different expression patterns in a range of candidate genes may act as a regulatory signal for a particular phenotype from a molecular genetic perspective. A molecular study was developed to validate the supernumerary teats characteristics. The second research phase includes a case-control application study to analyze the gene expression patterns of fibroblast growth factor 2 (FGF2) and expression of estrogen receptor 1 (ESR1) genes. The approach utilized standard laboratory techniques for RNA extraction, cDNA synthesis and cyber green dye-based gene expression quantification. When comparing two routine teat groups with four teats observation of the gene expression profile clearly shows the FGF2 gene pattern (P<0.01), There was no obvious difference in ESR1 gene response between the two experimental groups. This means that by combining promising gene expression tools, molecular approaches and evidence to validate gene expression in ewe carry supernumerary teats which will ultimately improve sheep production. Future research could provide valuable insights into the literature. [ABSTRACT FROM AUTHOR]

Background and purpose: after heart diseases and accidents, cancer is considered the third cause of death in Iran (1), and is a major health problem not only in Iran but also in many developed and developing countries. (2). Breast cancer is a disease in which breast cells grow out of control. This disease has different types based on the type of breast cells that become cancerous. Breast cancer accounts for about one-third of all types of cancer in the female population and is the main cause of cancer-related deaths in women worldwide (3). Estrogen receptor-α is one of the isoforms of estrogen receptor encoded by the ESR1 gene. ESR-α is a nuclear receptor that acts as a ligand-dependent transcription factor (4). After binding of estrogen, ESR-α binds to the estrogen response regions in the promoter of the target genes and causes changes in the expression of the target genes (5). The present study investigates the expression level of the estrogen receptor gene (ESR1) and long non-coding RNAs (lncRNAs) related to It investigates the allele frequency and genotype of single nucleotide polymorphism (SNP) rs2234693 in ESR1 gene in patients with breast cancer. Materials and methods: In this case-control study, the expression of ESR1 and related coding and non-coding RNAs were investigated by microarray (17 control samples and 104 patient samples), TCGA RNAseq (on 113 normal samples, 1102 primary tumors and seven Metastatic tumor samples) and data analysis was done by R Studio and limma, and ENCORI and GEPIA2 databases. Evaluation of microRNA interaction was done by miRWalk and lncRNA interaction finding was done by lncBase 3. Protein-protein interaction was analyzed by STRING and survival and correlation analysis by GEPIA2 and ENCORI. Pathway enrichment and gene ontology (GO) analyses were performed by KEGG and Enrichr and SNP analysis was performed by RFLP test. Results: ESR1 gene expression was increased in breast cancer and miR-15a-3p gene had a significant interaction with ESR1 and lncRNA OIP5-AS1. OIP5-AS1 and ESR1 had significant positive expression in patient samples. The frequency of TC, TT, and CC genotypes in healthy people was 65%, 15%, and 20%, respectively, and in the patient group it was 38.5%, 38.5% and 23%. There was a significant difference in the prevalence of ESR1 gene genotypes between patients and controls. Conclusion: ESR1 polymorphism may be associated with an increased risk of breast cancer and rs2234693 T>C SNP can be considered a strong marker for breast cancer screening. OIP5-AS1 may regulate breast cancer progression by altering ESR1 expression regulation.

Background and purpose: after heart diseases and accidents, cancer is considered the third cause of death in Iran (1), and is a major health problem not only in Iran but also in many developed and developing countries. (2). Breast cancer is a disease in which breast cells grow out of control. This disease has different types based on the type of breast cells that become cancerous. Breast cancer accounts for about one-third of all types of cancer in the female population and is the main cause of cancer-related deaths in women worldwide (3). Estrogen receptor-α is one of the isoforms of estrogen receptor encoded by the ESR1 gene. ESR-α is a nuclear receptor that acts as a ligand-dependent transcription factor (4). After binding of estrogen, ESR-α binds to the estrogen response regions in the promoter of the target genes and causes changes in the expression of the target genes (5). The present study investigates the expression level of the estrogen receptor gene (ESR1) and long non-coding RNAs (lncRNAs) related to It investigates the allele frequency and genotype of single nucleotide polymorphism (SNP) rs2234693 in ESR1 gene in patients with breast cancer. Materials and methods: In this case-control study, the expression of ESR1 and related coding and non-coding RNAs were investigated by microarray (17 control samples and 104 patient samples), TCGA RNAseq (on 113 normal samples, 1102 primary tumors and seven Metastatic tumor samples) and data analysis was done by R Studio and limma, and ENCORI and GEPIA2 databases. Evaluation of microRNA interaction was done by miRWalk and lncRNA interaction finding was done by lncBase 3. Protein-protein interaction was analyzed by STRING and survival and correlation analysis by GEPIA2 and ENCORI. Pathway enrichment and gene ontology (GO) analyses were performed by KEGG and Enrichr and SNP analysis was performed by RFLP test. Results: ESR1 gene expression was increased in breast cancer and miR-15a-3p gene had a significant interaction with ESR1 and lncRNA OIP5-AS1. OIP5-AS1 and ESR1 had significant positive expression in patient samples. The frequency of TC, TT, and CC genotypes in healthy people was 65%, 15%, and 20%, respectively, and in the patient group it was 38.5%, 38.5% and 23%. There was a significant difference in the prevalence of ESR1 gene genotypes between patients and controls. Conclusion: ESR1 polymorphism may be associated with an increased risk of breast cancer and rs2234693 T>C SNP can be considered a strong marker for breast cancer screening. OIP5-AS1 may regulate breast cancer progression by altering ESR1 expression regulation. [ABSTRACT FROM AUTHOR]

Simple Summary: Endocrine therapy (ET) remains the mainstay of treatment for Hormone Receptor-positive breast cancer, both in the early and advanced settings. The acquisition of mutations in the ESR1 gene encoding the estrogen receptor represents one of the main resistance mechanisms to ET. A conventional tumor tissue biopsy can be used to detect ESR1 mutations; however, these mutations are less likely to present on initial tissue biopsy, and such an invasive approach is hardly repeatable over time for longitudinal disease monitoring. The research of ESR1 mutations in liquid biopsies based on the analysis of circulating cell-free DNA in plasma is of increasing interest and has been recently recommended to guide therapy in patients with estrogen receptor-positive breast cancers at progression under ET. This comprehensive review reports the most recent advances and recommendations in this field and compares the different techniques available for the analysis of the ESR1 gene in liquid biopsy. The predominant forms of breast cancer (BC) are hormone receptor-positive (HR+) tumors characterized by the expression of estrogen receptors (ERs) and/or progesterone receptors (PRs). Patients with HR+ tumors can benefit from endocrine therapy (ET). Three types of ET are approved for the treatment of HR+ BCs and include selective ER modulators, aromatase inhibitors, and selective ER downregulators. ET is the mainstay of adjuvant treatment in the early setting and the backbone of the first-line treatment in an advanced setting; however, the emergence of acquired resistance can lead to cancer recurrence or progression. The mechanisms of ET resistance are often related to the occurrence of mutations in the ESR1 gene, which encodes the ER-alpha protein. As ESR1 mutations are hardly detectable at diagnosis but are present in 30% to 40% of advanced BC (ABC) after treatment, the timeline of testing is crucial. To manage this resistance, ESR1 testing has recently been recommended; in ER+ HER2− ABC and circulating cell-free DNA, so-called liquid biopsy appears to be the most convenient way to detect the emergence of ESR1 mutations. Technically, several options exist, including Next Generation Sequencing and ultra-sensitive PCR-based techniques. In this context, personalization of ET through the surveillance of ESR1 mutations in the plasma of HR+ BC patients throughout the disease course represents an innovative way to improve the standard of care. [ABSTRACT FROM AUTHOR]

It was attempted to molecularly characterize breast cancer patients of district Bannu, KP, Pakistan for any possible polymorphism in the estrogen receptor (ESR1) gene. Blood samples in this regard were collected from clinically diagnosed eighteen breast cancer patients, all possessing invasive ductal carcinoma. DNA was amplified through PCR for 2 different sequences of ESR1 gene. Twelve normal individuals of different ages were also characterized. Amplified products were digested with Xbal and Pvull restriction enzymes and were electrophoresed to visualize single nucleotide polymorphisms (SNPs); rs9340799 (G>A) and rs2234693 (C>T) in ESR1 gene. The amplified product of 524bp of rs9340799 sequence of ESR1 gene was treated with Xbal restriction enzyme while amplified product of 451bp of rs2234693 sequence was treated with PvuII restriction enzyme. Nine patients were found homozygous and 8 were heterozygous for minor allele while 1 patient was carrying major allele. For rs2234693, all the patients were carrying major allele. All the normal individuals were lacking the above stated 2 SNPs. There is thus strong correlation between SNPs of ESR1 gene and breast cancer and hence, can be used as a significant marker in the determination of breast cancer. [ABSTRACT FROM AUTHOR]

Recently multiple data accumulated concerning mutations in the ESR1 gene coding estrogen receptor α (mutESR1) and in the LYN gene coding non receptor tyrosine kinase SRC family member (mutLYN) that are associated with endocrine therapy resistance and that could be considered as markers of endocrine therapy efficiency. In case of gynecologic cancers including ovarian cancer the most frequent mutESR1 are ESR1L536H/P/R/V , ESR1Y537S/N/C/H, ESR1D538G that emerge in the course of hormonotherapy especially using aromatase inhibitors. mutLYN including LYNE159K, LYND189Y, LYNK209N, LYNA370T, LYNG418R, LYNA503D are also identified. mutESR1 and mutLYN increase transcriptional activity of estrogen receptor α (ERα) coded with ESR1 gene and catalytic activity of LYN kinase inducing endocrine therapy resistance. Interdependence of ESR1 and LYN genes is revealed at the level of proteins that they code as the kinases of the SRC family including LYN activate ERα-dependent transcription due to the phosphorylation of ERα at Y537 amino-acid residue that is the most frequently mutated in tumors with endocrine therapy resistance. The aim of the review is revealing the clinical correlations of mutESR1 and mutLYN with the ovarian cancer endocrine therapy resistance that opens perspectives of mutESR1 and mutLYN use as new predictive markers of ovarian cancer and development of more efficient anti-tumor medicaments. In the review the information obtained from PubMed database for the last 20 years using the following key words: ESR1, LYN, mutation(s), estrogen receptor α (ERα), LYN kinase, SRC family kinases, ovarian cancer, gynecologic(al) cancer is discussed.

Abstract Background Estrogens are essential for the development and proper function of several hormone-dependent organs. There are, however, several lines of evidence associating estrogens with mammary carcinogenesis. A marked individual genetic variability concerning estrogens biosynthesis, metabolism and mechanism of action was recognized and associated with human breast cancer susceptibility, clinical features and progression. Although some genetic variations in canine ESR1 gene were reported, their influence in clinicopathological features and progression of canine mammary tumors has not been fully evaluated. This study aims to assess the influence of SNPs in ESR1 gene (rs397512133, rs397510462, rs851327560, rs397510612, rs852887655, rs852684753 and rs852398698) in canine mammary tumors characteristics and progression. A group of 155 non-neutered bitches with mammary tumors was included in the study. Follow-up information was assessed 24 months after surgery. Results Genetic profiles associated with a later onset of mammary tumors and less aggressive clinicopathological features, namely smaller tumor size (≤ 3 cm) with extensive tubular differentiation and low canine-adapted prognostic index (vet-NPI), were identified in this study. Conclusions Our data suggest that the ESR1 genetic profile may help on the decision regarding the selection of individual tailored preventive measures against canine mammary tumors development, such as early neutering.

We studied the effect of functionally significant polymorphic markers of the ESR1 gene on the risk of breast cancer, tamoxifen resistance, and survival of patients with this type of cancer. The study included 239 primary breast cancer patients without distant metastases. The analysis of genotype frequency distribution for the studied ESR1 gene polymorphic markers showed the association of the rs2228480 and rs2234693 markers with tamoxifen resistance in the group of patients with luminal B type breast cancer. An association of these two polymorphic markers with the risk of tumor development was also revealed; for rs2234693 polymorphic marker, a relationship with the survival of patients was also showed. [ABSTRACT FROM AUTHOR]

Abstract Background The study investigated the associations of rs9340799:A > G (XbaI) and rs2234693:T > C (PvuII) polymorphisms in the estrogen receptor 1 gene (ESR1) with femoral neck (BMD-FN) and lumbar spine bone mineral density (BMD-LS), biochemical markers of bone turnover, calcium and phosphate levels, fracture prevalence, and a response to two types of anti-osteoporotic therapy in postmenopausal women from southern Slovakia. Methods We analysed 343 postmenopausal Slovak women (62.40 ± 0.46 years). The influence of rs9340799 (AA vs. AG + GG) and rs2234693 (TT vs. TC + CC) genotypes on BMD and biochemical markers was evaluated by covariance analysis adjusted for age and BMI. Binary logistic regression was used to evaluate the genotype effect on fracture prevalence. Pharmacogenetic part of the study included women who received a regular therapy of HT (17ß estradiol with progesterone; 1 mg/day for both; N = 76) or SERMs/raloxifene (60 mg/day; N = 64) during 48 months. The genotype-based BMD change was assessed by variance analysis for repeated measurements. Results Women with AA genotype of rs9340799 had higher BMD-FN (+ 0.12 ± 0.57 of T-score) and BMD-LS (+ 0.17 ± 0.08 of T-score) in comparison with AG + GG. The rs2234693 polymorphism did not affect any of the monitored parameters. No effect of any ESR1 polymorphisms was found on fracture prevalence. Both types of anti-osteoporotic therapy had a positive effect on BMD improvement in FN and LS sites. Considering the effect of the ESR1 gene within the HT, the subjects with rs9340799/AA genotype showed worse response than those with GG genotype (− 0.26 ± 0.10 of BMD-FN T-score; − 0.35 ± 0.10 of BMD-LS T-score) and also with AG genotype (− 0.22 ± 0.08 of BMD-LS T-score). The rs2234693/TT genotype responded poorer in BMD-LS in comparison with TC (− 0.22 ± 0.08 of T-score) and CC (− 0.35 ± 0.09 of T-score). The effect of the ESR1 gene on raloxifene therapy was reported only in BMD-LS. Subjects with rs9340799/AA genotype had a − 0.30 ± 0.11 of T-score worse response compared to AG genotype. The rs2234693/TT genotype showed − 0.39 ± 0.11 and − 0.46 ± 0.15 lower T-scores in comparison with TC and CC genotypes, respectively. Conclusions The rs9340799 polymorphism may contribute to decreased BMD in postmenopausal women from southern Slovakia; however, this is not related to higher fracture prevalence. Concurrently, both polymorphisms affected a response to analysed anti-osteoporotic therapies.

Objective: To obtain the key genes and signal pathways of diabetic peripheral neuropathy (DPN) through bioinformatics analysis of related gene chips in the GEO database. Methods: The DPN-related gene chip was downloaded from the GEO database, and the differential genes (DEGs) between DPN female patients and the normal control group were analyzed and visualized using R language. According to the gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG), DEGs were annotated, their functions and related pathways were predicted, and a protein interaction network was constructed using the STRING database to screen for core genes. Results: The analysis chip GSE95849 obtained 4746 DEGs of which 2218 genes were up-regulated and 2528 genes were down-regulated. Among them, TFAP2C, ESR1, CX3CR1, and FGL2 are at the core site of protein interaction. Conclusions: Differential genes are mainly involved in the MAPK pathway. They participate in the pathogenesis of DPN through blood glucose homeostasis, inflammatory effects, and neuronal development, providing new ideas for the diagnosis and treatment of DPN. [ABSTRACT FROM AUTHOR]

Genetic, immune and environmental factors are involved in preeclampsia (PE) etiopathogenesis. Considering that hypertension and poor placental perfusion are important features in PE, polymorphisms in the angiotensin-converting enzyme (ACE) and estrogen nuclear receptor 1 (ESR1) genes could be involved in the predisposition and/or development of the disease. The aim of this study was to evaluate if polymorphisms in ACE and ESR1 genes were associated with PE occurrence. This case-control study included 209 Brazilian pregnant women (107 with severe PE and 102 normotensive controls). The polymorphisms were investigated by polymerase chain reaction (PCR) followed by polyacrylamide gel electrophoresis. No significant difference between PE versus normotensive pregnant women, as well as early versus late PE, was observed when compared the allelic and genotypic frequencies of insertion/deletion polymorphism in intron 16 of the ACE gene and the single nucleotide polymorphisms (SNPs - rs2234693 and rs9340799) of the ESR1 gene. This pioneer study involving Brazilian women showed no association among the studied polymorphisms and PE, which suggests that ins/del ACE and SNPs ESR1 do not contribute to this disease occurrence in Brazil. • Hypertension and poor placental perfusion are important features in preeclampsia (PE). • Ins/del polymorphism in the angiotensin converting enzyme (ACE) gene is not associated with PE in Brazilian pregnant. • Frequency of Estrogen nuclear receptor1-ESR1 gene polymorphisms/rs2234693 and rs9340799 is not altered in Brazilian PE women. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the association of ESR1 rs2234693 and rs9340799 polymorphisms with radiographic defined knee osteoarthritis (OA), a case-control and meta-analysis was performed. Methods: A total of 25 case-control studies with 7,144 cases and 8,468 controls with were included. Results: There was a significant association between rs2234693 polymorphism and radiographic knee OA under heterozygote model (CT vs. TT: OR=1.164, 95% CI 1.053-1.286, p=0.003). However, there was no association between rs9340799 and radiographic knee OA. In subgroup analysis by ethnicity, risk estimates were not augmented. Conclusions: Our results showed that the ESR1 rs2234693 polymorphism might be associated with radiographic defined knee OA, but not rs9340799. [ABSTRACT FROM AUTHOR]

BACKGROUND: One of the major problems in IVF is the poor response of the ovary to gonadotropins. ESRI and FSHR are two effective genes on controlled ovarian hyperstimulation (COH). OBJECTIVES: Evaluating the correlation of alleles and genotypes of polymorphism (-29G/A) located in the FSH receptor gene and polymorphism (XbaI G/A) located in Estrogen receptor genes with the ovary’s response would help to anticipate the results of ovulation in IVF cycles. METHODS: In the present study, two hundred (200) blood samples were taken from infertile women aged 20 to 39 who were under IVF therapy. After DNA extraction from the samples, real-time PCR was performed using a specific probe-primer. RESULTS: Statistical analysis revealed that the frequency of alleles and genotypes of polymorphisms (-29G/A) and (XbaI A/G) in women with normal to poor response did not have significant correlation. [ABSTRACT FROM AUTHOR]

Background: Reproductive history and obesity are among the well-recognized risk factors in the development of breast cancer, which are partially mediated by the increased exposure of breast tissues to estrogens. However, only a few studies have investigated the link between these risk factors and the pattern of methylation signatures in the breast tissue of healthy women. The role of the estrogen receptor 1 ( ESR1) gene hypermethylation is reportedly important in the development of breast cancer. Thus, it is speculated that such ESR1 epigenetic changes may be influenced or shaped by obesity and reproductive history-related factors before and during breast carcinogenesis. Materials and Methods: Breast samples were collected from 120 cancer-free women who had undergone cosmetic mammoplasty. DNA was extracted from the breast tissues and, then, the methylation levels at the promoter and exon 1 regions of the ESR1 gene CpG island were determined by using the methylated DNA immunoprecipitation-quantitative PCR assay. Results: The methylation level of the ESR1 promoter observed in women with a body mass index (BMI) ≥30 kg/m2 ( p ≤ 0.001) was higher than in the subgroups of women of BMI <25 kg/m2 ( p < 0.001) and BMI 25-29 kg/m2 ( p < 0.001) and was also higher in postmenopausal women compared with that in premenopausal women ( p = 0.046). Pearson correlation coefficient analyses also showed that the high methylation of the ESR1 promoter was correlated with increasing age ( r = −0.246, p = 0.007) and BMI ( r = −0.331, p ≤ 0.001). Finally, linear multivariate regression revealed a significant association between high methylation rates in the ESR1 gene promoter and increased BMI (β = −0.285, 95% CI = −0.457 to −0.113, p = 0.001). Furthermore, a higher methylation level at the ESR1 gene exon 1 was found in the BMI ≥ 30 kg/m2 subgroup compared to the BMI 25-29 kg/m2 subgroup ( p = 0.023). Conclusion: These findings provide new hints about the relationship between epigenetic changes within the ESR1 gene CpG island and postmenopausal obesity and aging in cancer-free women. In terms of lifestyle intervention opportunities, this study also highlights the significance and feasibility of such interventions for BMI as a modifiable risk factor. [ABSTRACT FROM AUTHOR]

Single-nucleotide polymorphism (SNP) association studies have become crucial in uncovering the genetic correlations of genomic variants with complex diseases, quantitative traits and physiological responses to drugs. However, the identification of SNPs responsible for specific phenotypes is a difficult problem to solve, requiring multiple testing of hundreds or thousands of SNPs in candidate genes. In this study, we performed an analysis of the genetic variations that can alter the structure and function of oestrogen receptor α using different computational tools. Among the nonsynonymous SNPs, a total of four SNPs were found to be damaging by both a sequence homology-based tool (SIFT) and a structural homology-based method (polyphen-2, SNAP), as well as by the ESEfinder program, and one nonsense nsSNP was found. For noncoding SNPs, we found that one SNP in 5 UTR may potentially change protein expression level, nine SNPs were found to affect miRNA binding site and 28 SNPs might affect transcriptional regulation of the ESR1 gene. Reviewing the literature, 89 SNPs were found to be functional among which only four were located in exons. [ABSTRACT FROM AUTHOR]

Objectives. Sex steroids are important regulators of bone physiology and play an essential role in the maintenance of bone health throughout the life. Hormonal replacement therapy (HRT) is a treatment commonly used to relieve symptoms and some undesirable consequences of menopause such as osteoporosis. Osteoporosis, characterized by the loss of bone mass and deterioration of microarchitecture with a consequent higher risk of fragility fractures, is under genetic influence. A tetranucleotide (TTTA)n microsatellite repeat polymorphism, at intron 4 of the CYP19 (aromatase) gene, has been previously associated with higher lumbar spine bone mineral density (LS-BMD) and lower risk of spine fracture in postmenopausal women. Moreover, the ERα encoded by the ESR1 gene is another important candidate for the regulation of bone mass of menopause. Moreover prospective analysis from >18.000 subjects at the GENOMOS study indicated that XX homozygotes genotype had a reduced risk of fracture independently from BMD. In the present study, we investigated in postmenopausal Italian women, at baseline and after 1 year of HRT, whether ESR1 and CYP19 gene polymorphisms could affect BMD through different statistical models. Methods. This study has been performed on 100 post-menopausal Italian women, from a larger group of 250. The study group was administred HRT and LS-BMD was measured at baseline and after 1 year of therapy. Genetic analysis evaluating ESR1 and CYP19 gene polymorphisms was performed. Results. Generalized Linear Models (GLMs) test showed that women with normal LS-BMD at the baseline had a major statistically significant BMD increase of 0.1426 gr/cm² (p= 0.0001) with respect to the osteoporotic patients. In addition, subjects with genotype 1 and 2 of CYP19 gene had a lower modification in LS-BMD after 1 year of HRT (0.0837 gr/cm² and 0,076 g/cm²; p=0.0470 and 0,0547 respectively) when compared to genotype 3. No influences of the aromatase genotypes were observed in the variable difference using both Anova and GLMs test. Regarding the ESR1 gene polymorphism, the LS-BMD after 1 year of HRT was influenced by the diagnosis at the baseline and height and ERa genotypes were able to influence difference with statistical significant results with both test. Conclusions. In the present study, we have demonstrated that CYP19 gene polymorphism is able to influence the effect of 1 year HRT on LS-BMD with no influence on pre-/ and post-/HRT LS-BMD differences. Although ESR1 gene polymorphism is not able to influence the LS-BMD after 1 year HRT, it influences the observed modifications during the year of therapy. These data underlie the complexity of the genetics of the bone mass and its importance in influencing the response to HRT. [ABSTRACT FROM AUTHOR]

Endometriosis is a steroid-dependent complex disease. The oestrogen receptor plays an important rote by mediating oestrogen action and eutopic or ectopic endometrium development. This study investigated whether sing[e-nucleotide polymorphisms in the genes for oestrogen receptor 1 (ESR1) and oestrogen receptor 2 (ESR2) are associated with endometriosis and endometriosis-related infertility. The participants included 157 infertile and 155 fertile endometriosis women as welt as 92 women with primary infertility and 265 fertile women as controls. The iPLEX Gold system (MassARRAY system, Sequenom) was used for genotyping of ESR1 and ESR2. Statistical analysis showed that ESRI (rs3798573 A/G) was significantly associated with endometriosis and endometriosis-related infertility (P = 0.011, P = 0.009). No association was found with ESRI (rsl 159327 A/G, rs3020348 A/C) and ESR2 (rs17179740 A/G) either for endometriosis or endometriosis-related infertility. According to the revised American Fertility Society classification, all of the detected single-nucleotide polymorphisms had no association with endometriosis in stage I-II or in stage III-IV. The results suggest that the ESRI polymorphism rs3798573 A/G is associated with increased risk of endometriosis and endometriosis-related infertility in Han women from central China. [ABSTRACT FROM AUTHOR]

Abstract: The estrogen receptor is one of the most important transcription factors in breast tumor growth and development. We, and others, have previously shown that hypoxia induces rapid ERα protein degradation by a proteasome-mediated pathway in breast cancer cells, which is linked with ERα activation. However, no report has shown the effect of hypoxia on ESR1 gene regulation at the transcriptional level. In this report, we show that hypoxia repressed the expression of ERα mRNA in MCF-7 and T47D human breast cancer cells, but not in human endometrial Ishikawa cells, although ERα degradation under hypoxia was also observed in Ishikawa cells. This indicates that ESR1 transcriptional repression and ERα protein downregulation by hypoxia are regulated by distinct mechanisms. Repression of ESR1 gene transcription occurred at the transcriptional level as a result of decreased recruitment of RNA polymerase II at the proximal promoter of the ESR1 locus in response to stabilization of the HIF-1α protein under hypoxia. Our data show that hypoxia induces repression of the ESR1 gene, which may facilitate hormone insensitivity in the tumor microenvironment. [Copyright &y& Elsevier]

The present study was undertaken to analyze the expression pattern of estrogen receptor 1 gene (ESR1) in Barbari bucks (fertile and non-fertile) identified on the basis of seminal quality traits and fertility trials. RNA was extracted from the spleen by Trizol method. The expression pattern of ESR1 gene was analyzed using real time polymerase chain reaction (RT-PCR). The expression pattern of ESR1 gene was analyzed by RT-PCR (Roche LC-480). Relative quantification by RT-PCR indicated that the ESR1 gene expression showed more fold in fertile bucks as compared to non-fertile. [ABSTRACT FROM AUTHOR]

Estrogen insensitivity syndrome (EIS) arises from rare mutations in estrogen receptor-α (ERα, encoded by ESR1 gene) resulting in the inability of estrogen to exert its biological effects. Due to its rarity, mutations in ESR1 gene and the underlying molecular mechanisms of EIS have not been thoroughly studied. Here, we investigate known ESR1 mutants, Q375H and R394H, associated with EIS patients using in vitro and in vivo systems. Comparison of the transcriptome and deoxyribonucleic acid methylome from stable cell lines of both Q375H and R394H clinical mutants shows a differential profile compared with wild-type ERα, resulting in loss of estrogen responsiveness. Molecular dynamic simulation shows that both ESR1 mutations change the ERα conformation of the ligand-receptor complexes. Furthermore, we generated a mouse model Esr1-Q harboring the human mutation using CRISPR/Cas9 genome editing. Female and male Esr1-Q mice are infertile and have similar phenotypes to αERKO mice. Overall phenotypes of the Esr1-Q mice correspond to those observed in the patient with Q375H. Finally, we explore the effects of a synthetic progestogen and a gonadotropin-releasing hormone inhibitor in the Esr1-Q mice for potentially reversing the impaired female reproductive tract function. These findings provide an important basis for understanding the molecular mechanistic consequences associated with EIS., (Published by Oxford University Press on behalf of the Endocrine Society 2020.)

Objective: The aim: To evaluate the association between estrogen receptor (ESR1) α- Xbal polymorphism with estradiol serum blood level in the patients with premenstrual syndrome., Patients and Methods: Materials and methods: 50 women with premenstrual syndrome and 20 controls were examined. The level of estradiol was measured in the blood serum in both phases of the menstrual cycle by ELISA method. Polymerase chain reaction was used to study ESR1 gene polymorphism (A-351G variant)., Results: Results: The estradiol concentration was similar in two phases of the menstrual cycle between healthy women and patients with premenstrual syndrome. But the more growth of estradiol in the luteal phase was determined in the persons with premenstrual syndrome. The rate of GG genotype was the largest in women with severe premenstrual syndrome (χ2=3.52, p=0.06). Also, in the persons with severe premenstrual syndrome who had G allele (GG+AG genotype) the estradiol concentration in the luteal phase of the menstrual cycle was on 50.00 % (p=0.02) higher compared to carriers of AA genotype. There was no difference in estradiol level between healthy women with GG+AG genotype and AA genotype., Conclusion: Conclusions: AG polymorphism of ESR1 gene may be the marker of development of premenstrual syndrome.

Estrogen receptor (ER) α-positive breast cancers frequently acquire resistance to endocrine therapy. However, recent studies found that a fraction of these tumors overexpress ER, and that estrogen treatment induces apoptosis. We propose a 'cancer navigation' strategy to systematically lead resistant cells to growth arrest and apoptosis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: One of the major problems in IVF is the poor response of the ovary to gonadotropins. ESRI and FSHR are two effective genes on controlled ovarian hyperstimulation (COH)., Objectives: Evaluating the correlation of alleles and genotypes of polymorphism (-29G/A) located in the FSH receptor gene and polymorphism (XbaI G/A) located in Estrogen receptor genes with the ovary's response would help to anticipate the results of ovulation in IVF cycles., Methods: In the present study, two hundred (200) blood samples were taken from infertile women aged 20 to 39 who were under IVF therapy. After DNA extraction from the samples, real-time PCR was performed using a specific probe-primer., Results: Statistical analysis revealed that the frequency of alleles and genotypes of polymorphisms (-29G/A) and (XbaI A/G) in women with normal to poor response did not have significant correlation.

ESR1 has been listed in the Human Obesity Gene Map as candidate gene associated with obesity. Thus, in this study, we investigated the effect of the ESR1 rs1884051 polymorphism on obesity-related variables, together with their modulations by dietary intake in Korean men. The obesity-related variables and dietary intake of 3,039 Korean men aged 40-59 years from KoGES database were analyzed. Body weight (P = 0.007), BMI (P = 0.003), waist-hip ratio (= 0.011), fat body mass (P = 0.010), and body fat percentage (P = 0.040) were significantly lower in subjects with the minor T allele of ESR1 rs1884051 than in subjects carrying the C allele. Moreover, the rs1884051 T allele was associated with a decreased risk of obesity prevalence (P = 0.040). Among the subjects whose total energy intake was below the median, carrier of the minor T allele of ESR1 rs1884051 had a lower BMI (P = 0.003) when compared with subjects carrying the C allele. In addition, among subjects whose plant protein intake was above the median, carrier of the minor T allele of ESR1 rs1884051 had a lower BMI (P = 0.044) compared with subjects carrying the C allele. Our findings demonstrate that there is a significant association between the ESR1 rs1884051 variant and obesity-related variables and this association can be potentially modified by dietary energy and plant protein intake.