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1.
J Environ Manage ; 301: 113708, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34619591

RESUMO

Estrone (E1), 17α-estradiol (17α-E2), 17ß-estradiol (17ß-E2), and estriol (E3) are persistent in livestock manure and present serious pollution concerns because they can trigger endocrine disruption at part-per-trillion levels. This study conducted a global analysis of estrogen occurrence in manure using all literature data over the past 20 years. Besides, predicted environmental concentration (PEC) in soil and water was estimated using fate models, and risk/harm quotient (RQ/HQ) methods were applied to screen risks on children as well as on sensitive aquatic and soil species. The estradiol equivalent values ranged from 6.6 to 4.78 × 104 ng/g and 12.4 to 9.46 × 104 ng/L in the solid and liquid fraction. The estrogenic potency ranking in both fractions were 17ß-E2> E1>17α-E2>E3. RQs of measured environmental concentration in the liquid fraction pose medium (E3) to high risk (E1, 17α-E2 & 17ß-E2) to fish but are lower than risks posed by xenoestrogens. However, the RQ of PECs on both soil organisms and aquatic species were insignificant (RQ < 0.01), and HQs of contaminated water and soil ingestion were within acceptable limits. Nevertheless, meticulous toxicity studies are still required to confirm (or deny) the findings because endocrine disruption potency from mixtures of these classes of compounds cannot be ignored.


Assuntos
Esterco , Poluentes Químicos da Água , Animais , Criança , Monitoramento Ambiental , Estradiol/toxicidade , Estrogênios/análise , Estrogênios/toxicidade , Estrona/análise , Humanos , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidade
2.
Sci Total Environ ; 803: 150042, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-34525709

RESUMO

Although four major natural estrogens (i.e., estrone (E1), 17ß-estradiol (E2), estriol (E3) and 17α-estradiol (αE2)) have been commonly found in livestock urine, this study reports the occurrence of eight other less-studied natural estrogens in urine of swine and cattle, i.e. 2-hydroxyestone (2OHE1), 4-hydroxyestrone (4OHE1), 2-hydroxyestradiol (2OHE2), 4-hydroxyestradiol (4OHE2), 16-epiestriol (16epiE3), 16α-hydroxyestrone (16αE1), 16-ketoestradiol (16ketoE2), and 17epiestriol (17epiE3). Results showed that each estrogen was found in at least one urine sample, and 6 of 8 the less-studied estrogens were present at frequencies of ≥90% in boars, ≥70% in sows, and ≥50% in dairy cattle. Five of eight the less-studied estrogens were present at frequencies of ≥33.3% in four beef cattle and one bull. On a concentration basis, the 8 less-studied natural estrogens represented 73.2%, 85.2%, 39.9%, 47.7%, 26.9%, 56.0% and 44.1% of total concentrations of the twelve natural estrogens when combining data from all animals. Similar results were observed based on estrogen equivalence, which indicated these newly detected eight less-studied natural estrogens were not negligible. This work is the first to figure out the importance of these less-studied natural estrogens in livestock urine, and their potential environmental risks associated with discharge of livestock wastewater should be urgently assessed in a holistic manner.


Assuntos
Estrogênios , Estrona , Animais , Bovinos , Estradiol , Feminino , Gado , Masculino , Suínos , Águas Residuárias
3.
Sci Total Environ ; 802: 149913, 2022 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-34474298

RESUMO

Reports have highlighted the presence of PCBs and their metabolites, OH-PCBs, in human serum as well as their endocrine-disrupting effects on reproductive function through direct interactions with the androgen receptor (AR) and estrogen receptor (ER). However, the molecular mechanisms directly linking the actions of PCBs and OH-PCBs on the AR and ER to induce reproductive impairment remain poorly understood. In this study, we characterized the cellular response to PCBs and OH-PCBs acting on AR and ER transactivation at the transcriptome level coupled with bioinformatics analysis to identify the downstream pathways of androgen and estrogen signaling that leads to reproductive dysfunction. We first confirmed the agonistic and antagonistic effects of several PCBs and OH-PCBs on AR- and ER-mediated reporter gene activity using the androgen-responsive LNCaP and estrogen-responsive MCF-7 cell lines, respectively. Anti-estrogenic activity was not detected among the tested compounds; however, we found that in addition to anti-androgenic and estrogenic activity, PCB 28 and PCB 138 exhibited androgenic activity, while most of the tested OH-PCBs showed a synergistic effect on DHT-mediated transactivation of the AR. Bioinformatics analysis of transcriptome profiles from selected PCBs and OH-PCBs revealed various pathways that were dysregulated depending on their agonistic, antagonistic, or synergistic effects. The OH-PCBs with estrogenic activity affected pathways including vitamin metabolism and calcium transport. Other notable dysregulated pathways include cholesterol transport in response to androgenic PCBs, thyroid hormone metabolism in response to anti-androgenic PCBs, and antioxidant pathways in response to androgen-synergistic OH-PCBs. Our results demonstrate that PCBs and OH-PCBs directly alter specific pathways through androgen- or estrogen-mediated signaling, thereby providing additional insights into the mechanisms by which these compounds cause reproductive dysfunction.


Assuntos
Bifenilos Policlorados , Reprodução , Estrogênios , Humanos , Células MCF-7 , Bifenilos Policlorados/toxicidade , Receptores Androgênicos , Receptores de Estrogênio/genética , Reprodução/efeitos dos fármacos , Transdução de Sinais , Transcriptoma
4.
Sci Total Environ ; 805: 150058, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-34537690

RESUMO

The co-occurrence of cyanobacterial harmful algal blooms and contaminants is an increasing environmental concern in freshwater worldwide. Our field investigations coupled with laboratory incubations demonstrated that the microbial degradation potential of 17ß-estradiol (E2) with estrone as the intermediate was primarily driven by increased dissolved organic matter (DOM) in the water column of a cyanobacterial bloom. To explain the intrinsic contribution of cyanobacterial-derived DOM (C-DOM) to estrogen biodegradation, a combination of methods including bioassay, ultrahigh-resolution mass spectrometry, and microbial ecology were applied. The results showed that preferential assimilation of highly biodegradable structures, including protein-, carbohydrate-, and unsaturated hydrocarbon-like molecules sustained bacterial growth, selected for more diverse microbes, and resulted in greater estrogen biodegradation compared to less biodegradable molecules (lignin- and tannin-like molecules). The biodegradability of C-DOM decreased from 78% to 1%, whereas the E2 biodegradation rate decreased dramatically at first, then increased with the accumulation of recalcitrant, bio-produced lipid-like molecules in C-DOM. This change was linked to alternative substrate-induced selection of the bacterial community under highly refractory conditions, as suggested by the greater biomass-normalized E2 biodegradation rate after a 24-h lag phase. In addition to the increased frequency of potential degraders, such as Sphingobacterium, the network analysis revealed that C-DOM molecules distributed in high H/C (protein- and lipid-like molecules) were the main drivers structuring the bacterial community, inducing strong deterministic selection of the community assemblage and upregulating the metabolic capacity for contaminants. These findings provide strong evidence that estrogen biodegradation in eutrophic water may be facilitated by cyanobacterial blooms and provide a theoretical basis for ecological remediation of estrogen pollution.


Assuntos
Cianobactérias , Lagos , Estrogênios , Estrona , Água
5.
Biomed Res Int ; 2021: 7702863, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34734086

RESUMO

People who receive the ChAdOx1 nCoV-19 vaccine, particularly perimenopausal women who are on birth control or postmenopausal women who take estrogen supplements, may experience thrombosis and thrombocytopenia. Estrogen and the ChAdOx1 nCoV-19 vaccine both have the potential to cause thrombus in different ways. Some postmenopausal women who are also taking estrogens may develop thrombosis and thrombocytopenia after receiving the ChAdOx1 nCoV-19 vaccine. Therefore, women are encouraged to stop taking drugs containing estrogen before receiving this vaccine. Furthermore, consuming fish oil can help reduce the risk of developing blood clots among women who are in the luteal phase and, thus, have high estrogen levels. In addition, ChAdOx1 nCoV-19's side effects in young women could be mitigated by administering it during the follicular phase.


Assuntos
Vacinas contra COVID-19/efeitos adversos , COVID-19 , Estrogênios/administração & dosagem , Trombose/etiologia , Vacinação/efeitos adversos , Feminino , Humanos , Menopausa , SARS-CoV-2 , Trombocitopenia/etiologia
6.
Environ Monit Assess ; 193(12): 812, 2021 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-34786612

RESUMO

The aim of the present study was to investigate steroid hormone residues from livestock farms and assess their risks to the surface water of Phayao Lake. These steroid hormones are endocrine-disrupting compounds (EDCs), which can be found in natural and synthetic forms. This research focused on examining the residues of seven steroid hormones (five estrogens and two androgens-estrone (E1), 17α-estradiol (αE2), 17ß-estradiol (ßE2), estriol (E3), 17α-ethinyl estradiol (EE2), testosterone (T), and 17α-methyltestosterone (MT)) from four types of livestock farms around Phayao Lake, Thailand. The samples collected from the livestock farms included feces, soil, and wastewater and were extracted by the solid phase extraction (SPE) technique and analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). The risks from the residual steroid hormones were also characterized by estradiol equivalents (EEQs), testosterone equivalents (TEQs), and risk quotients (RQs). The results indicated that most hormone contamination from the farms' livestock was due to the estrogen hormones E1 (1.38-97.10 ng/g), ßE2 (10.08-1366 ng/g), and EE2 (1.50-99.92 ng/g), which originate from the natural excretion and admixture of steroids in feedstock or medicines. Steroid hormones were not detected in the wastewater from cleaning processes on farms with wastewater treatment plants, whereas farms without wastewater treatment plants showed high values of estrogen hormone contamination, with EEQs of 128.8-472.9 ng/L and RQs of 208.3-294.3. However, the analysis of steroid hormone residues in Phayao Lake demonstrated that the residues did not severely affect aquatic organisms (with RQs of 0.002-144.5), and no estrogen or androgen residues were observed in the water treatment plant or tap water.


Assuntos
Lagos , Poluentes Químicos da Água , Androgênios , Animais , Cromatografia Líquida , Monitoramento Ambiental , Estrogênios/análise , Estrona/análise , Fazendas , Gado , Espectrometria de Massas em Tandem , Tailândia , Poluentes Químicos da Água/análise
7.
Maturitas ; 154: 13-19, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34736575

RESUMO

OBJECTIVES: To compare the effect of oral estradiol (E2) plus vaginal progesterone (P4) against placebo on endometrial thickness, endometrial biopsy pathology, cervical cytology and total cancer incidence among healthy postmenopausal women. STUDY DESIGN: This study is a sub-analysis of the Early versus Late Intervention Trial with Estradiol (ELITE), a randomized, double-blinded, placebo-controlled trial that previously demonstrated that hormone therapy (HT) was associated with less progression of subclinical atherosclerosis than placebo when therapy was initiated within 6 years after menopause but not when it was initiated 10 or more years after menopause. This sub-analysis included only ELITE participants with an intact uterus, who were randomized to either daily oral micronized 17-beta-E2 1 mg/day with 4% vaginal micronized P4 gel 45 mg/day for 10 days each month or placebo. MAIN OUTCOME MEASURES: Participants were evaluated at baseline and annually during a median follow-up of 4.8 years for endometrial thickness as determined by pelvic transvaginal ultrasound followed by an endometrial biopsy when indicated, and cervical cytology and cancer incidence. RESULTS: Over up to 80 months of follow-up, participants randomized to oral E2 plus vaginal P4 had progressive and statistically significant increases in endometrial thickness (p<0.001), underwent more endometrial biopsies and had a higher rate of endometrial hyperplasia on endometrial biopsy compared with the placebo group. Due to the close follow-up of participants in the trial protocol, these abnormal findings were effectively treated. CONCLUSION: Our results suggest that 10 days of vaginal P4 45 mg/day is insufficient to completely oppose the effect of oral E2 1 mg/day on the endometrium. Further studies are needed to test alternative doses or frequencies of administration of vaginal P4 for adequate endometrial protection from E2 therapy among postmenopausal women. ClinicalTrials.gov registration NCT00114517.


Assuntos
Endométrio/efeitos dos fármacos , Estradiol/administração & dosagem , Estrogênios/administração & dosagem , Pós-Menopausa/efeitos dos fármacos , Progesterona/administração & dosagem , Idoso , Método Duplo-Cego , Hiperplasia Endometrial/induzido quimicamente , Hiperplasia Endometrial/epidemiologia , Endométrio/metabolismo , Estradiol/uso terapêutico , Estrogênios/uso terapêutico , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Progesterona/uso terapêutico , Resultado do Tratamento
8.
Pediatrics ; 148(5)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34620727

RESUMO

BACKGROUND AND OBJECTIVES: Referrals of transgender and gender-diverse (trans) youth to medical clinics for gender-affirming care have increased. We described characteristics of trans youth in Canada at first referral visit. METHODS: Baseline clinical and survey data (2017-2019) were collected for Trans Youth CAN!, a 10-clinic prospective cohort of n = 174 pubertal and postpubertal youth <16 years with gender dysphoria, referred for hormonal suppression or hormone therapy, and 160 linked parent-participants. Measures assessed health, demographics, and visit outcome. RESULTS: Of youth, 137 were transmasculine (assigned female) and 37 transfeminine (assigned male); 69.0% were aged 14 to 15, 18.8% Indigenous, 6.6% visible minorities, 25.7% from immigrant families, and 27.1% low income. Most (66.0%) were gender-aware before age 12. Only 58.1% of transfeminine youth lived in their gender full-time versus 90.1% of transmasculine (P < .001). Although transmasculine youth were more likely than transfeminine youth to report depressive symptoms (21.2% vs 10.8%; P = .03) and anxiety (66.1% vs 33.3%; P < .001), suicidality was similarly high overall (past-year ideation: 34.5%, attempts: 16.8%). All were in school; 62.0% reported strong parental gender support, with parents the most common support persons (91.9%). Two-thirds of families reported external gender-related stressors. Youth had met with a range of providers (68.5% with a family physician). At clinic visit, 62.4% were prescribed hormonal suppression or hormone therapy, most commonly depot leuprolide acetate. CONCLUSIONS: Trans youth in Canada attending clinics for hormonal suppression or gender-affirming hormones were generally healthy but with depression, anxiety, and support needs.


Assuntos
Disforia de Gênero , Encaminhamento e Consulta , Pessoas Transgênero , Adolescente , Conscientização , Canadá , Criança , Depressão/diagnóstico , Estrogênios/uso terapêutico , Feminino , Disforia de Gênero/tratamento farmacológico , Disforia de Gênero/psicologia , Identidade de Gênero , Nível de Saúde , Antagonistas de Hormônios/uso terapêutico , Humanos , Povos Indígenas/estatística & dados numéricos , Leuprolida/uso terapêutico , Masculino , Pobreza/estatística & dados numéricos , Estudos Prospectivos , Meio Social , Ideação Suicida , Tentativa de Suicídio/estatística & dados numéricos , Testosterona/uso terapêutico , Pessoas Transgênero/psicologia , Pessoas Transgênero/estatística & dados numéricos
9.
Nutrients ; 13(10)2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34684335

RESUMO

About 20-30% of premenopausal women have metabolic syndrome, and the number is almost double in postmenopausal women, and these women have an increased risk of hepatosteatosis. Postmenopausal women with metabolic syndrome are often treated with hormone replacement therapy (HRT), but estrogens in currently available HRTs increase the risk of breast and endometrial cancers and Cardiovascular Disease. Therefore, there is a critical need to find safer alternatives to HRT to improve postmenopausal metabolic health. Pathway preferential estrogen 1 (PaPE-1) is a novel estrogen receptor ligand that has been shown to favorably affect metabolic tissues without adverse effects on reproductive tissues. In this study, we have examined the effects of PaPE-1 on metabolic health, in particular, examining its effects on the liver transcriptome and on plasma metabolites in two different mouse models: diet-induced obesity (DIO) and leptin-deficient (ob/ob) mice. PaPE-1 significantly decreased liver weight and lipid accumulation in both DIO and ob/ob models and lowered the expression of genes associated with fatty acid metabolism and collagen deposition. In addition, PaPE-1 significantly increased the expression of mitochondrial genes, particularly ones associated with the electron transport chain, suggesting an increase in energy expenditure. Integrated pathway analysis using transcriptomics and metabolomics data showed that PaPE-1 treatment lowered inflammation, collagen deposition, and pathways regulating fatty acid metabolism and increased metabolites associated with glutathione metabolism. Overall, our findings support a beneficial metabolic role for PaPE-1 and suggest that PaPE-1 may protect postmenopausal women from fatty liver disease without increasing reproductive cancer risk.


Assuntos
Dieta Hiperlipídica , Estrogênios/uso terapêutico , Fígado Gorduroso/etiologia , Fígado Gorduroso/prevenção & controle , Ovariectomia , Animais , Peso Corporal/efeitos dos fármacos , Colágeno/metabolismo , Receptor alfa de Estrogênio/metabolismo , Estrogênios/farmacologia , Fígado Gorduroso/complicações , Fígado Gorduroso/genética , Células Hep G2 , Hepatócitos/metabolismo , Humanos , Inflamação/patologia , Ligantes , Metabolismo dos Lipídeos , Fígado/metabolismo , Metabolômica , Camundongos Endogâmicos C57BL , Camundongos Obesos , Obesidade/complicações , Obesidade/genética , Tamanho do Órgão/efeitos dos fármacos , Transcriptoma/genética , Ganho de Peso
10.
Molecules ; 26(20)2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34684681

RESUMO

Bisphenol A (BPA) is a typical environmental endocrine disruptor that exhibits estrogen-mimicking, hormone-like properties and can cause the collapse of bone homeostasis by an imbalance between osteoblasts and osteoclasts. Various BPA substitutes, structurally similar to BPA, have been used to manufacture 'BPA-free' products; however, the regulatory role of BPA alternatives in osteoclast differentiation still remains unelucidated. This study aimed to investigate the effects of these chemicals on osteoclast differentiation using the mouse osteoclast precursor cell line RAW 264.7. Results confirmed that both BPA and its alternatives, bisphenol F and tetramethyl bisphenol F (TMBPF), were nontoxic to RAW 264.7 cells. In particular, tartrate-resistant acid phosphatase (TRAP)-positive multinucleated cell staining and activity calculation assays revealed that TMBPF enhanced osteoclast differentiation upon stimulation of the receptor activator of nuclear factor-kappa B ligand (RANKL). Additionally, TMBPF activated the mRNA expression of osteoclast-related target genes, such as the nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), tartrate-resistant acid phosphatase (TRAP), and cathepsin K (CtsK). Western blotting analysis indicated activation of the mitogen-activated protein kinase signaling pathway, including phosphorylation of c-Jun N-terminal kinase and p38. Together, the results suggest that TMBPF enhances osteoclast differentiation, and it is critical for bone homeostasis and skeletal health.


Assuntos
Compostos Benzidrílicos/farmacologia , Estrogênios não Esteroides/farmacologia , Osteoblastos/efeitos dos fármacos , Fenóis/farmacologia , Animais , Reabsorção Óssea , Diferenciação Celular/efeitos dos fármacos , Estrogênios/análogos & derivados , Estrogênios/farmacologia , Macrófagos/efeitos dos fármacos , Camundongos , Proteínas Quinases Ativadas por Mitógeno/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Células RAW 264.7 , Transdução de Sinais/efeitos dos fármacos
11.
Behav Neurol ; 2021: 5346507, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34594430

RESUMO

Epidemiological studies have suggested that traumatic stress increases vulnerability to various mental disorders, such as dementia and psychiatric disorders. While women are more vulnerable than men to depression and anxiety, it is unclear whether endogenous estrogens are responsible for the underlying sex-specific mechanisms. In this study, the aromatase gene heterozygous (Ar+/-) mice were used as an endogenous estrogen deficiency model and age- and sex-matched wild type mice (WT) as controls to study the predator odor 2,3,5-trimethyl-3-thiazoline- (TMT-) induced short- and long-term cognitive and social behavior impairments. In addition, the changes in brain regional neurotransmitters and their associations with TMT-induced changes in behaviors were further investigated in these animals. Our results showed TMT induced immediate fear response in both Ar+/- and WT mice regardless of sexes. TMT induced an acute impairment of novel object recognition memory and long-term social behavior impairment in WT mice, particularly in females, while Ar+/- mice showed impaired novel object recognition in both sexes and TMT-elevated social behaviors, particularly in males. TMT failed to induce changes in the prepulse inhibition (PPI) test in both groups. TMT resulted in a slight increase of DOPAC/DA ratio in the cortex and a significant elevation of this ratio in the striatum of WT mice. In addition, the ratio of HIAA/5-HT was significantly elevated in the cortex of TMT-treated WT mice, which was not found in TMT-treated Ar+/- mice. Taken together, our results indicate that TMT exposure can cause cognitive and social behavior impairments as well as change catecholamine metabolism in WT mice, and endogenous estrogen deficiency might desensitize the behavioral and neurochemical responses to TMT in Ar+/- mice.


Assuntos
Medo , Odorantes , Animais , Aromatase/genética , Comportamento Animal , Cognição , Estrogênios , Feminino , Humanos , Masculino , Camundongos , Comportamento Social
12.
Orphanet J Rare Dis ; 16(1): 453, 2021 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-34715881

RESUMO

BACKGROUND: Intracardiac leiomyomatosis (ICLM) is a rare life-threatening form of intravenous leiomyomatosis (IVLM). The incomplete resection and recurrence are associated with high morbidity and mortality. The objective of this study is to identify that whether estrogen deprivation therapies, including bilateral salpingo-oophorectomy (BSO)-based surgery and gonadotrophin releasing hormone agonists (GnRHa) administration, could bring benefits to patients with primary unresectable ICLM. METHODS: PubMed/MEDLINE (Ovid) was searched (up to May 2021) for studies reporting individual patient data on demographics, clinicopathological features, treatment, and follow-up information. Exclusion criteria were patients who may have been included in two or more publications. This study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: A total of 114 patients from 70 papers were included. Several reports showed that the tumor in the right atrium and inferior vena cava shrank dramatically after BSO-based surgery, or GnRHa administrated preoperatively in premenopausal women. The rate of complete resection was 64.04% in patients with ICLM, which was 85.25% in no/slight adhesion and no pulmonary nodules group, while 22.22% in firm/extensive adhesion and/or pulmonary nodules group (p < 0.0001). Meanwhile, the recurrence rates in patients with complete resection and incomplete resection were 4.29% and 37.84% respectively (p < 0.0001). Furthermore, complete resection with BSO had the lowest recurrence rate of 3.13%, incomplete resection with BSO had a progression rate of 45.45%, while incomplete resection with ovarian preservation had the highest progression rate of 75.00%. CONCLUSIONS: The recurrence rate of ICLM was closely related to firm/extensive adhesion in IVC or above, and/or pulmonary nodules. BSO-based surgery might reduce the recurrence rate no matter ICLM could be completely resected or not. In addition, estrogen deprivation therapies could decrease tumor burden as a primary treatment, and further make a secondary complete resection feasible in premenopausal women with initially unresectable ICLM.


Assuntos
Leiomiomatose , Estrogênios/uso terapêutico , Feminino , Humanos , Leiomiomatose/tratamento farmacológico , Leiomiomatose/cirurgia , Recidiva Local de Neoplasia/tratamento farmacológico , Veia Cava Inferior
13.
Chem Biol Interact ; 350: 109685, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34653397

RESUMO

The increasing levels of estrogens and pollution by other steroids pose considerable challenges to the environment. In this study, the genome of Gordonia polyisoprenivorans strain R9, one of the most effective 17 beta-estradiol- and steroid-degrading bacteria, was sequenced and annotated. The circular chromosome of G. polyisoprenivorans R9 was 6,033,879 bp in size, with an average GC content of 66.91%. More so, 5213 putative protein-coding sequences, 9 rRNA, 49 tRNA, and 3 sRNA genes were predicted. The core-pan gene evolutionary tree for the genus Gordonia showed that G. polyisoprenivorans R9 is clustered with G. polyisoprenivorans VH2 and G. polyisoprenivorans C, with 93.75% and 93.8% similarity to these two strains, respectively. Altogether, the three G. polyisoprenivorans strains contained 3890 core gene clusters. Strain R9 contained 785 specific gene clusters, while 501 and 474 specific gene clusters were identified in strains VH2 and C, respectively. Furthermore, whole genome analysis revealed the existence of the steroids and estrogens degradation pathway in the core genome of all three G. polyisoprenivorans strains, although the G. polyisoprenivorans R9 genome contained more specific estrogen and steroid degradation genes. In strain R9, 207 ABC transporters, 95 short-chain dehydrogenases (SDRs), 26 monooxygenases, 21 dioxygenases, 7 aromatic ring-hydroxylating dioxygenases, and 3 CoA esters were identified, and these are very important for estrogen and steroid transport, and degradation. The results of this study could enhance our understanding of the role of G. polyisoprenivorans R9 in estradiol and steroid degradation as well as evolution within the G. polyisoprenivorans species.


Assuntos
Actinobacteria/genética , Actinobacteria/metabolismo , Poluentes Ambientais/metabolismo , Estradiol/metabolismo , Esteroides/metabolismo , Actinobacteria/classificação , Animais , Composição de Bases , Biodegradação Ambiental , Disruptores Endócrinos/metabolismo , Estrogênios/metabolismo , Genoma Bacteriano , Humanos , Família Multigênica , Filogenia , Especificidade da Espécie
14.
Anal Chem ; 93(41): 13998-14006, 2021 10 19.
Artigo em Inglês | MEDLINE | ID: mdl-34612624

RESUMO

Overexpression of estrogen receptors (ERs) is one of the important characteristics of most breast cancers. We aim to develop a new type of ER-specific radioiodine-labeled estrogen derivative ([131I]IPBA-EE), which was modified with an albumin-specific ligand 4-(p-iodophenyl) butyric acid (IPBA) to improve the metabolic stability and enhance the ER-targeting ability of estrogen. [131I]IPBA-EE can effectively bind to albumin in vitro, and its dissociation constant (Kd = 0.31 µM) is similar to IPBA (Kd = 0.30 µM). The uptake of [131I]IPBA-EE in ER-positive MCF-7 cells (41.81 ± 3.41%) was significantly higher than that in ER-negative MDA-MB-231 cells (8.78 ± 2.37%, ***P < 0.0005) and could be significantly blocked (3.92 ± 0.35%, ***P < 0.0005). The uptakes of [131I]IPBA-EE in rat uterus and ovaries were 5.66 ± 0.34% ID/g and 5.71 ± 2.77% ID/g, respectively, at 1 h p.i., and these uptakes could be blocked by estradiol (uterus: 2.81 ± 0.41% ID/g, *P < 0.05; ovarian: 3.02 ± 0.08% ID/g, *P < 0.05). SPECT/CT imaging showed that ER-positive MCF-7 tumor uptake of [131I]IPBA-EE reached to 6.07 ± 0.20% ID/g at 7 h p.i., which was significantly higher than that of ER-negative MDA-MB-231 tumor (0.87 ± 0.08% ID/g, **P < 0.005) and could be blocked obviously with fulvestrant (1.65 ± 1.56% ID/g, *P < 0.05). In conclusion, a novel radioiodinated estradiol derivative, [131I]IPBA-EE with albumin-binding property and good metabolic stability, was developed to image the ER in breast cancer. This promising ER-targeted probe has the potential to warrant further preclinical investigations.


Assuntos
Neoplasias da Mama , Estradiol , Animais , Neoplasias da Mama/diagnóstico por imagem , Ácido Butírico , Estrogênios , Feminino , Humanos , Radioisótopos do Iodo , Ratos , Distribuição Tecidual , Tomografia Computadorizada de Emissão de Fóton Único
15.
Int J Mol Sci ; 22(19)2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34638643

RESUMO

Elevated intraocular pressure (IOP) is the only modifiable risk factor for primary open-angle glaucoma (POAG). Herein we sought to prioritize a set of previously identified IOP-associated genes using novel and previously published datasets. We identified several genes for future study, including several involved in cytoskeletal/extracellular matrix reorganization, cell adhesion, angiogenesis, and TGF-ß signaling. Our differential correlation analysis of IOP-associated genes identified 295 pairs of 201 genes with differential correlation. Pathway analysis identified ß-estradiol as the top upstream regulator of these genes with ESR1 mediating 25 interactions. Several genes (i.e., EFEMP1, FOXC1, and SPTBN1) regulated by ß-estradiol/ESR1 were highly expressed in non-glaucomatous human trabecular meshwork (TM) or Schlemm's canal (SC) cells and specifically expressed in TM/SC cell clusters defined by single-cell RNA-sequencing. We confirmed ESR1 gene and protein expression in human TM cells and TM/SC tissue with quantitative real-time PCR and immunofluorescence, respectively. 17ß-estradiol was identified in bovine, porcine, and human aqueous humor (AH) using ELISA. In conclusion, we have identified estrogen receptor signaling as a key modulator of several IOP-associated genes. The expression of ESR1 and these IOP-associated genes in TM/SC tissue and the presence of 17ß-estradiol in AH supports a role for estrogen signaling in IOP regulation.


Assuntos
Estrogênios/genética , Pressão Intraocular/genética , Transdução de Sinais/genética , Animais , Humor Aquoso/fisiologia , Bovinos , Linhagem Celular , Matriz Extracelular/genética , Glaucoma de Ângulo Aberto/genética , Humanos , Suínos , Malha Trabecular/fisiologia
16.
BMC Musculoskelet Disord ; 22(1): 891, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34670550

RESUMO

BACKGROUND: Rotator cuff (RC) tears represent a common cause of shoulder pain and dysfunction in adults. The disease affects primarily women and occurs mainly in the postmenopausal period. This study aimed to investigate immunohistochemically the presence of estrogen receptor-alpha (ER-⍺), estrogen receptor-beta (ER-ß) and progesterone receptor (PR) in the supraspinatus tendon of patients with RC tendinopathy, searching for gender differences of expression. A secondary aim was to evaluate potential links between their expression and the typical histopathological findings of the ailment. METHODS: Biopsies of the supraspinatus tendon were collected intraoperatively from 15 postmenopausal women and 9 men undergoing RC surgery. Specimens were stained with Haematoxylin/Eosin, Masson-Goldner Trichrome, Alcian Blu and immunohistochemical stainings for ER-⍺, ER-ß and PR were performed. Tendon alterations were evaluated with the Bonar histopathological scale. Statistical tests used in this study were the Spearman correlation coefficient and the Mann-Whitney U test. RESULTS: In the supraspinatus tendon, cells expressed ER-⍺ (p = 0.043), ER-ß (p = 0.048) and PR (p = 0.004) with statistically significant differences related to age and sex of patients. Immunoreactivity was seen in the nuclei of tenocytes and vascular cells. Postmenopausal women's samples showed a markedly higher expression of these receptors compared to their male counterpart. There was a positive correlation between the expression of ER-⍺ and ER-ß (r = 0.59; p = 0.02) and between ER-ß and PR (r = 0.72; p = 0.002) in women's samples. Furthermore, in postmenopausal women the PR expression decreased with age (r = - 0.56; p = 0.027). Only in women, the ER-ß expression positively correlated with the total Bonar histopathological score (p = 0.019) and the ER-ß vascular expression positively correlated with ground substance alterations (p = 0.029). CONCLUSIONS: These results reveal that ERs and PR are present in the supraspinatus tendon of patients with RC tears, suggesting a role of sex hormones in the pathogenesis of the disease.


Assuntos
Receptores de Estrogênio/metabolismo , Receptores de Progesterona , Lesões do Manguito Rotador/metabolismo , Estrogênios , Feminino , Humanos , Masculino , Estudos Retrospectivos
17.
Clin Obstet Gynecol ; 64(4): 721-738, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34668886

RESUMO

Combined hormonal contraception (CHC) are short-acting, reversible methods containing both estrogen and progestin. Available CHC methods include combined oral contraceptives, transdermal patches, and vaginal rings. The combined oral contraceptive remains the most commonly used contraceptive method in the United States. The general principles of CHC will be reviewed, including mechanism of action and effectiveness. Unless otherwise stated, these principles apply to all CHCs. When discussing clinical studies and specific considerations related only to pills, patches, or rings, the method(s) will be specified. Words that specify sex are used when discussing studies in which sex was specified.


Assuntos
Anticoncepcionais Orais Hormonais , Progestinas , Anticoncepção , Anticoncepcionais Orais Combinados/efeitos adversos , Estrogênios , Feminino , Contracepção Hormonal , Humanos
18.
Exp Suppl ; 112: 341-361, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34687016

RESUMO

Glycosylation within the immunoglobulin G (IgG) Fc region modulates its ability to engage complement and Fc receptors, affording the opportunity to fine-tune effector functions. Mechanisms regulating IgG Fc glycans remain poorly understood. Changes accompanying menarche, menopause, and pregnancy have long implicated hormonal factors. Intervention studies now confirm that estrogens enhance IgG Fc galactosylation, in females and also in males, defining the first pathway modulating Fc glycans and thereby a new link between sex and immunity. This mechanism may participate in fetal-maternal immunity, antibody-mediated inflammation, and other aspects of age- and sex-specific immune function. Here we review the changes affecting the IgG Fc glycome from childhood through old age, the evidence establishing a role for estrogens, and research directions to uncover associated mechanisms that may inform therapeutic intervention.


Assuntos
Fragmentos Fc das Imunoglobulinas , Imunoglobulina G , Estrogênios , Feminino , Glicosilação , Humanos , Fragmentos Fc das Imunoglobulinas/genética , Fragmentos Fc das Imunoglobulinas/metabolismo , Imunoglobulina G/metabolismo , Masculino , Gravidez , Receptores Fc/genética , Receptores Fc/metabolismo
19.
J Headache Pain ; 22(1): 119, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34620097

RESUMO

BACKGROUND: Migraine is a common neurological disease with extremely debilitating, but fully reversible symptoms. Women suffer from migraine more often than men. It was assumed that fluctuation of oestrogen level during menstrual cycle is one of many factors responsible for more frequent migraine attacks. The second-to-fourth digit ratio (2D:4D) is considered as an indicator of prenatal sex steroids. Balance of prenatal androgens (testosterone) and oestrogen has been studied in numerous diseases that are affected by hormones. However, the relationship between migraine and the sex steroids balance in prenatal development is still unexplained. The aim of this paper is to provide an evidence of relationship between prenatal oestrogen and testosterone exposure following 2D:4D digit ratio, and migraine prevalence in adults. METHODS: We examined a group of 151 adults (33 males, 118 females) with migraine and a control group of 111 adults (45 males, 66 females). 2D:4D digit ratio of both hands was measured using sliding Vernier calliper. RESULTS: Significant differences were found in the right hand. Female migraineurs had lower value of 2D:4D ratio than the control group and the right 2D:4D was lower than left 2D:4D (Δ2D:4D), suggesting prenatal testosterone dominance. The opposite relationship was observed in males. Male migraineurs had higher value of 2D:4D ratio and Δ2D:4D was greater than the control group, suggesting prenatal oestrogen dominance. CONCLUSIONS: Our results suggest that depending on sex, different proportion of prenatal sex steroids might be a risk factor of migraine in adults. Women with migraine were presumably exposed in prenatal life to higher testosterone levels relative to oestrogen, while men with migraine were probably exposed in prenatal life to higher levels of oestrogen relative to testosterone.


Assuntos
Transtornos de Enxaqueca , Testosterona , Adulto , Estrogênios , Feminino , Hormônios Esteroides Gonadais , Humanos , Masculino , Transtornos de Enxaqueca/epidemiologia , Fatores de Risco
20.
Front Cell Infect Microbiol ; 11: 702628, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34660336

RESUMO

Menopause in human females and subsequent ovarian hormone deficiency, particularly concerning 17ß-estradiol (E2), increase the risk for metabolic dysfunctions associated with obesity, diabetes type 2, cardiovascular diseases, and dementia. Several studies indicate that these disorders are also strongly associated with compositional changes in the intestinal microbiota; however, how E2 deficiency and hormone therapy affect the gut microbial community is not well understood. Using a rat model, we aimed to evaluate how ovariectomy (OVX) and subsequent E2 administration drive changes in metabolic health and the gut microbial community, as well as potential associations with learning and memory. Findings indicated that OVX-induced ovarian hormone deficiency and E2 treatment had significant impacts on several health-affecting parameters, including (a) the abundance of some intestinal bacterial taxa (e.g., Bifidobacteriaceae and Porphyromonadaceae), (b) the abundance of microbial short-chain fatty acids (SCFAs) (e.g., isobutyrate), (c) weight/BMI, and (d) high-demand spatial working memory following surgical menopause. Furthermore, exploratory correlations among intestinal bacteria abundance, cognition, and BMI underscored the putative influence of surgical menopause and E2 administration on gut-brain interactions. Collectively, this study showed that surgical menopause is associated with physiological and behavioral changes, and that E2-linked compositional changes in the intestinal microbiota might contribute to some of its related negative health consequences. Overall, this study provides novel insights into interactions among endocrine and gastrointestinal systems in the post-menopausal life stage that collectively alter the risk for the development and progression of cardiovascular, metabolic, and dementia-related diseases.


Assuntos
Microbioma Gastrointestinal , Animais , Estrogênios , Feminino , Menopausa , Obesidade , Ratos , Memória Espacial
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