estrogen metabolism
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PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0261362
Author(s):  
Nhung Le ◽  
Melissa Cregger ◽  
Veronica Brown ◽  
Julio Loret de Mola ◽  
Pamela Bremer ◽  
...  

Endometriosis is an estrogen dependent gynecological disease associated with altered microbial phenotypes. The association among endogenous estrogen, estrogen metabolites, and microbial dynamics on disease pathogenesis has not been fully investigated. Here, we identified estrogen metabolites as well as microbial phenotypes in non-diseased patients (n = 9) and those with pathologically confirmed endometriosis (P-EOSIS, n = 20), on day of surgery (DOS) and ~1–3 weeks post-surgical intervention (PSI). Then, we examined the effects of surgical intervention with or without hormonal therapy (OCPs) on estrogen and microbial profiles of both study groups. For estrogen metabolism analysis, liquid chromatography/tandem mass spectrometry was used to quantify urinary estrogens. The microbiome data assessment was performed with Next generation sequencing to V4 region of 16S rRNA. Surgical intervention and hormonal therapy altered gastrointestinal (GI), urogenital (UG) microbiomes, urinary estrogen and estrogen metabolite levels in P-EOSIS. At DOS, 17β-estradiol was enhanced in P-EOSIS treated with OCPs. At PSI, 16-keto-17β-estradiol was increased in P-EOSIS not receiving OCPs while 2-hydroxyestradiol and 2-hydroxyestrone were decreased in P-EOSIS receiving OCPs. GI bacterial α-diversity was greater for controls and P-EOSIS that did not receive OCPs. P-EOSIS not utilizing OCPs exhibited a decrease in UG bacterial α-diversity and differences in dominant taxa, while P-EOSIS utilizing OCPs had an increase in UG bacterial α-diversity. P-EOSIS had a strong positive correlation between the GI/UG bacteria species and the concentrations of urinary estrogen and its metabolites. These results indicate an association between microbial dysbiosis and altered urinary estrogens in P-EOSIS, which may impact disease progression.


2021 ◽  
Vol 12 ◽  
Author(s):  
Ya-Lun Han ◽  
Zhi-Hui Sun ◽  
Shuai Chang ◽  
Bin Wen ◽  
Jian Song ◽  
...  

Sea urchin (Strongylocentrotus intermedius) is an economically important mariculture species in Asia, and its gonads are the only edible part. The efficiency of genetic breeding in sea urchins is hampered due to the inability to distinguish gender by appearance. In this study, we first identified a sex-associated single nucleotide polymorphism (SNP) by combining type IIB endonuclease restriction site-associated DNA sequencing (2b-RAD-seq) and genome survey. Importantly, this SNP is located within spata4, a gene specifically expressed in male. Knocking down of spata4 by RNA interference (RNAi) in male individuals led to the downregulation of other conserved testis differentiation-related genes and germ cell marker genes. We also revealed that sex ratio in this validated culture population of S. intermedius is not 1:1. Moreover, after a 58-day feeding experiment with estradiol, the expression levels of several conserved genes that are related to testis differentiation, ovary differentiation, and estrogen metabolism were dynamically changed. Taken together, our results will contribute toward improving breeding efficiency, developing sex-controlled breeding, and providing a solid base for understanding sex determination mechanisms in sea urchins.


2021 ◽  
Author(s):  
Xiaomin Li ◽  
Ling Fang ◽  
Hongjiang Li ◽  
Xiaoqin Yang

Background: In China, the association between estrogen metabolism and breast cancer risk and the differences in metabolic pattern between breast cancer patients and controls are poorly understood. Methods: A total of 84 patients with invasive breast cancer and 47 controls with benign breast diseases were included in this study. Estrogen metabolites from their morning urine were determined by HPLC-MS/MS and evaluated in both groups, and the predictive value of each estrogen metabolite in the malignant group according to their menstrual status was analyzed. Results: Urinary concentration of estrogen metabolites 2-OHE1, 2-OHE2, 4-OHE2, 4-MeOE1, and 16ɑ-OHE1 were lower in postmenopausal patients with breast cancer, compared with benign controls, In logistic regression model, breast cancer risk increased with the decline in the levels of 4-OHE2 and 4-MeOE1. In premenopausal patients,, a difference in the level of 2-OHE2 was observed between both groups, and 2-OHE2 was found to have predictive value for breast cancer. Additionally, urinary 2-OHE2 level in premenopausal HR+ patients was considerably higher compared with HR- patients. Conclusions: We found that lower urinary levels of 4-OHE2 and 4-MeOE1had predictive value for breast cancer, and higher 2-OHE1 were associated with HR+ breast cancer in premenopausal women.


2021 ◽  
Author(s):  
Junjie Hu ◽  
lele zhang ◽  
Haoran Xia ◽  
Yilv Yan ◽  
Xinsheng Zhu ◽  
...  

Abstract Immunotherapy has revolutionized cancer treatment, but most patients are refractory to immunotherapy or acquire resistance. To explore immunotherapy resistance mechanisms, we characterized the transcriptomes of ~92000 single cells from 15 patients with non-small cell lung cancer (NSCLC) during neoadjuvant PD-1 blockade combined with chemotherapy. CD8+ T, natural killer, B, and dendritic cells were activated by therapy. Therapy also promoted differentiation of memory T cells into effector T cells. Macrophages were remodeled into an M0-like phenotype and neutrophils into an aged phenotype. Distinct therapy-induced cancer-cell transcriptomes were associated with clinical response. Major pathologic responders (MPRs) activated antigen presentation via major histocompatibility complex class II (MHC-II). Cancer cells of non-MPRs exhibited overexpression of estrogen metabolism enzymes and elevated serum estradiol. Elevated estradiol activated EGFR signaling and upregulated the expression of VEGFA, which promoted an immunosuppressive microenvironment. FCRL4+FCRL5+ memory B cells and CD16+CX3CR1+ monocytes were identified as biomarkers for positive immunotherapy response.


2021 ◽  
Vol 8 ◽  
Author(s):  
David E. Williams

Hydrolysis of glucobrassicin by plant or bacterial myrosinase produces multiple indoles predominantly indole-3-carbinol (I3C). I3C and its major in vivo product, 3,3'-diindolylmethane (DIM), are effective cancer chemopreventive agents in pre-clinical models and show promise in clinical trials. The pharmacokinetics/pharmacodynamics of DIM have been studied in both rodents and humans and urinary DIM is a proposed biomarker of dietary intake of cruciferous vegetables. Recent clinical studies at Oregon State University show surprisingly robust metabolism of DIM in vivo with mono- and di-hydroxylation followed by conjugation with sulfate or glucuronic acid. DIM has multiple mechanisms of action, the most well-characterized is modulation of aryl hydrocarbon receptor (AHR) signaling. In rainbow trout dose-dependent cancer chemoprevention by dietary I3C is achieved when given prior to or concurrent with aflatoxin B1, polycyclic aromatic hydrocarbons, nitrosamines or direct acting carcinogens such as N-methyl-N'-nitro-nitrosoguanidine. Feeding pregnant mice I3C inhibits transplacental carcinogenesis. In humans much of the focus has been on chemoprevention of breast and prostate cancer. Alteration of cytochrome P450-dependent estrogen metabolism is hypothesized to be an important driver of DIM-dependent breast cancer prevention. The few studies done to date comparing glucobrassicin-rich crucifers such as Brussels sprouts with I3C/DIM supplements have shown the greater impact of the latter is due to dose. Daily ingestion of kg quantities of Brussels sprouts is required to produce in vivo levels of DIM achievable by supplementation. In clinical trials these supplement doses have elicited few if any adverse effects. Sulforaphane from glucoraphanin can act synergistically with glucobrassicin-derived DIM and this may lead to opportunities for combinatorial approaches (supplement and food-based) in the clinic.


2021 ◽  
Author(s):  
Xiaoyan Liu ◽  
Xiaoyi Tian ◽  
Qinghong Shi ◽  
Haidan Sun ◽  
Jing Li ◽  
...  

Abstract Previous studies reported that gender, age, diets or lifestyles could influence urine metabolomics, which should be considered in biomarker discovery. As a consequence, for the baseline of urine metabolomics characteristics, it becomes critical to avoid confounding effects in clinical cohort studies. In this study, we provided a comprehensive characterization of urine metabolomics in a cohort of 348 healthy children (Aged 1~18) and 315 adults (Aged 20-78) for evaluation gender and age effects. Our results suggested that urine metabolites showed larger gender differences in children than in adults. For both male/boy and female/girl, each age group showed specific metabolic characterization. Especially, the pantothenate and CoA biosynthesis and alanine metabolism pathways were enriched in early life. Androgen and estrogen metabolism showed high activity during adolescence and youth stages. Pyrimidine metabolism was enriched in the old stage. This work could help us understand the baseline of urine metabolism characteristics and contribute to further studies of clinical disease biomarker discovery.


2021 ◽  
Vol 8 ◽  
Author(s):  
Yanan Sun ◽  
Shreya Sangam ◽  
Qiang Guo ◽  
Jian Wang ◽  
Haiyang Tang ◽  
...  

Pulmonary arterial hypertension (PAH) is a complex and devastating disease with a poor long-term prognosis. While women are at increased risk for developing PAH, they exhibit superior right heart function and higher survival rates than men. Susceptibility to disease risk in PAH has been attributed, in part, to estrogen signaling. In contrast to potential pathological influences of estrogen in patients, studies of animal models reveal estrogen demonstrates protective effects in PAH. Consistent with this latter observation, an ovariectomy in female rats appears to aggravate the condition. This discrepancy between observations from patients and animal models is often called the “estrogen paradox.” Further, the tissue-specific interactions between estrogen, its metabolites and receptors in PAH and right heart function remain complex; nonetheless, these relationships are essential to characterize to better understand PAH pathophysiology and to potentially develop novel therapeutic and curative targets. In this review, we explore estrogen-mediated mechanisms that may further explain this paradox by summarizing published literature related to: (1) the synthesis and catabolism of estrogen; (2) activity and functions of the various estrogen receptors; (3) the multiple modalities of estrogen signaling in cells; and (4) the role of estrogen and its diverse metabolites on the susceptibility to, and progression of, PAH as well as their impact on right heart function.


2021 ◽  
Vol 30 (03) ◽  
pp. 222-229
Author(s):  
Matthias Hackl ◽  
Elisabeth Semmelrock ◽  
Johannes Grillari

AbstractMicroRNAs (miRNAs) are short (18–24 nucleotides) non-coding RNA sequences that regulate gene expression via binding of messenger RNA. It is estimated that miRNAs co-regulate the expression of more than 70% of all human genes, many of which fulfil important roles in bone metabolism and muscle function. In-vitro and in-vivo experiments have shown that the targeted loss of miRNAs in distinct bone cell types (osteoblasts and osteoclasts) results in altered bone mass and bone architecture. These results emphasize the biological relevance of miRNAs for bone health.MiRNAs are not only considered as novel bone biomarkers because of their biological importance to bone metabolism, but also on the basis of other favorable properties: 1) Secretion of miRNAs from cells enables “minimally invasive” detection in biological fluids such as serum. 2) High stability of miRNAs in serum enables the retrospective analysis of frozen blood specimens. 3) Quantification of miRNAs in the serum is based on the RT-PCR - a robust method that is considered as the gold standard for the analysis of nucleic acids in clinical diagnostics.With regard to osteoporosis, it has been shown that many of the known risk factors are characterized by distinct miRNA profiles in the affected tissues: i) age-related loss of bone mass, ii) sarcopenia, iii) changes in estrogen metabolism and related changes Loss of bone mass, and iv) diabetes. Therefore, numerous studies in recent years have dealt with the characterization of miRNAs in the serum of osteoporosis patients and healthy controls, and were able to identify recurring miRNA patterns that are characteristic of osteoporosis. These novel biomarkers have great potential for the diagnosis and prognosis of osteoporosis and its clinical outcomes.The aim of this article is to give a summary of the current state of knowledge on the research and application of miRNA biomarkers in osteoporosis.


Author(s):  
Beata Starek-Świechowicz ◽  
Bogusława Budziszewska ◽  
Andrzej Starek

AbstractBreast cancer is the most common female malignancy and the second leading cause of cancer related deaths. It is estimated that about 40% of all cancer in women is hormonally mediated. Both estrogens and androgens play critical roles in the initiation and development of breast cancer. Estrogens influence normal physiological growth, proliferation, and differentiation of breast tissues, as well as the development and progression of breast malignancy. Breast cancer is caused by numerous endo- and exogenous risk factors. The paper presents estrogen metabolism, in particular 17β-estradiol and related hormones. The mechanisms of estrogen carcinogenesis include the participation of estrogen receptors, the genotoxic effect of the estrogen metabolites, and epigenetic processes that are also presented. The role of reactive oxygen species in breast cancer has been described. It called attention to a role of numerous signaling pathways in neoplastic transformation. Chemoprotective agents, besides other phytoestrogens, classical antioxidants, synthetic compounds, and their mechanisms of action have been shown.


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