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1.
Artigo em Inglês | MEDLINE | ID: mdl-32582576

RESUMO

COVID-19 morbidity and mortality have significant gender disparities, with higher prevalence and mortality in men. SARS-CoV-2 enters the lungs through the ACE2 enzyme, a member of the renin-angiotensin system (RAS). Although there are no data for the lung, the expressions of RAS components in other tissues are modulated by sex hormones, androgens, and estrogens. However, there are no data on sex-specific differences in ACE2 expression. If there is a sex difference in the expression of ACE2 in the lung, this could theoretically explain the gender disparity in COVID-19 disease. More importantly, although modulation of ACE2 will certainly not provide a cure for the COVID-19 disease, modulation of ACE2 by sex hormone modulators, if they affect the expression of ACE2, could potentially be developed into a supportive therapy for COVID-19 patients.


Assuntos
Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/mortalidade , Peptidil Dipeptidase A/metabolismo , Pneumonia Viral/epidemiologia , Pneumonia Viral/mortalidade , Androgênios/sangue , Betacoronavirus , Infecções por Coronavirus/patologia , Estrogênios/sangue , Feminino , Humanos , Pulmão/metabolismo , Masculino , Pandemias , Pneumonia Viral/patologia , Distribuição por Sexo , Fatores Sexuais
2.
Gene ; 740: 144535, 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32156529

RESUMO

Many human epidemiology and animal model studies have reported that bisphenol A (BPA) exerts adverse effects on reproduction through different regulatory mechanisms and signaling pathways in adults. In recent years, the exposure risk has increased for the general population, and little is known about how BPA affects ovarian development in adolescent animals and humans. In the present study, we aimed to investigate the effects of BPA exposure on ovarian development and the transcriptome in adolescent mice. Four-week-old ICR female mice were randomly divided into two groups and orally administered BPA (200 ng/kg/day) by gavage for 4 weeks. The BPA and estrogen (E2) levels in sera from the two groups were subsequently determined by using enzyme-linked immunosorbent assays (ELISAs). An immunohistochemical study showed that several obvious ovarian structural and developmental abnormalities were observed in the treatment group with changes in the E2 receptor gene and protein expression levels. A total of 4266 differentially expressed genes (DEGs) were identified, and the possible functions of these DEGs were explored by bioinformatics analyses based on the RNA-Seq data. The two most significant expression profiles were identified by Short Time-series Expression Miner (STEM) software, and the genes in these two profiles were enriched in actin filament-based processes, behaviour and membrane potential regulation according to Gene Ontology (GO) enrichment analysis. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that these DEGs are particularly involved in the endocrine system, the calcium and cAMP signaling pathways.


Assuntos
Compostos Benzidrílicos , Ovário/efeitos dos fármacos , Ovário/crescimento & desenvolvimento , Fenóis , Maturidade Sexual/efeitos dos fármacos , Animais , Compostos Benzidrílicos/sangue , Compostos Benzidrílicos/metabolismo , Compostos Benzidrílicos/toxicidade , Receptor beta de Estrogênio/genética , Receptor beta de Estrogênio/metabolismo , Estrogênios/sangue , Estrogênios/metabolismo , Feminino , Perfilação da Expressão Gênica , Imuno-Histoquímica , Camundongos , Ovário/ultraestrutura , Fenóis/sangue , Fenóis/metabolismo , Fenóis/toxicidade
3.
Gynecol Oncol ; 156(2): 400-406, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31813586

RESUMO

OBJECTIVE: Blood-based biomarkers are attractive due to ease of sampling and standardized measurement technology, reducing obstacles to clinical implementation. The objective of this study was to evaluate a clinically available method of steroid hormone measurement for its prognostic potential in endometrial cancer. METHODS: We quantified seven steroid hormones by liquid chromatography-tandem mass spectrometry in 100 endometrial cancer patients from a prospective cohort. Abdominal fat distribution was assessed from abdominal computed tomography (CT) scans. Steroid hormone levels were compared to clinical characteristics, fat distribution and gene expression in primary tumor samples. RESULTS: Low levels of 17OH-progesterone, 11-deoxycortisol and androstenedione were associated with aggressive tumor characteristics and poor disease specific survival (p = .003, p = .001 and p = .02 respectively). Adjusting for preoperative risk based on histological type and grade, low 17OH-progesterone and 11-deoxycortisol independently predicted poor outcome with hazard ratios of 2.69 (p = .033, 95%CI: 1.09-6.68) and 3.40 (p = .020, 1.21-9.51), respectively. Tumors from patients with low steroid level displayed increased expression of genes related to mitosis and cell cycle progression, whereas high steroid level was associated with upregulated estrogen signaling and genes associated with inflammation. Estrone and estradiol correlated to abdominal fat volume in all compartments (total, visceral, subcutaneous, p < .001 for all), but not to the visceral fat proportion. Patients with higher levels of circulating estrogens had increased expression of estrogen signaling related genes. CONCLUSION: Low levels of certain endogenous steroids are associated with aggressive tumor traits and poor survival and may provide preoperative information independent of histological biomarkers already in use.


Assuntos
17-alfa-Hidroxiprogesterona/sangue , Androstenodiona/sangue , Cortodoxona/sangue , Neoplasias do Endométrio/sangue , Estrogênios/sangue , Biomarcadores Tumorais/sangue , Carcinoma Endometrioide/sangue , Carcinoma Endometrioide/genética , Carcinoma Endometrioide/mortalidade , Cromatografia Líquida , Estudos de Coortes , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/mortalidade , Estradiol/sangue , Estrona/sangue , Feminino , Expressão Gênica , Humanos , Noruega/epidemiologia , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Transdução de Sinais , Espectrometria de Massas em Tandem
4.
Artigo em Inglês | MEDLINE | ID: mdl-31689897

RESUMO

Menopause, the permanent cessation of the menstrual cycle, marks the end of a woman's reproductive lifespan. Menopausal hormonal therapy (MHT) can potentially skew the fatty acid profile increasing the risk for developing metabolic diseases and disorders of skeletal, gastrointestinal, and nervous systems. The aim of this study was to investigate the fatty acid profile of postmenopausal women receiving, and not receiving, hormone replacement therapy. A total of 156 healthy women with a mean age of 60 participated in this cross-sectional study. Gas chromatography with an Agilent Technologies 7890A GC system was used to determine fatty acid content. Statistical analysis was conducted using R software, version 3.4.1. Women receiving MHT had significantly higher (p < 0.05) concentrations of C14:0 and C16:0. MHT was found to be associated with a tendency (p = 0.053) to diminish concentrations of C18:1n-9, C20:4, and all unsaturated fatty acids (p < 0.05). The longer MHT was used, the higher the concentration of C24:1 (p = 0.04) and the lower the concentration of C18:2n-6 (p = 0.03).


Assuntos
Estrogênios/sangue , Ácidos Graxos/sangue , Terapia de Reposição Hormonal/estatística & dados numéricos , Pós-Menopausa/sangue , Adulto , Estudos Transversais , Ácidos Graxos/análise , Feminino , Humanos , Pessoa de Meia-Idade
5.
Artigo em Inglês | MEDLINE | ID: mdl-31671514

RESUMO

Aging causes a decline in physical function and hormonal balance. Exercise can improve these parameters. However, the beneficial effects of a combined exercise program (Korean dance and yoga) on physical function and hormonal status in elderly women remain unknown. This study aims to investigate the effects of a 12-week combined exercise program on balance, flexibility, muscle strength, and hormonal status in elderly Korean women. Twenty-five healthy elderly women were recruited and randomly divided into the control (CON) and exercise (EXE) groups. The EXE group underwent the combined exercise program (60 min/day and 3 times/week) for 12 weeks. The two groups did not differ in body weight, lean body mass, fat mass, body fat percentage, or body mass index at baseline or in the changes following the experimental conditions. A significant time × group interaction was detected for anterior and posterior dynamic balance, static balance, and growth hormone (GH). After the combined exercise program, anterior dynamic balance, posterior dynamic balance, static balance, flexibility, muscle strength, GH, dehydroepiandrosterone-sulfate, and estrogen significantly increased in the EXE group compared to the CON group. In conclusion, the combined exercise program contributed to improvements in overall health, including physical function and hormonal status, in elderly Korean women.


Assuntos
Envelhecimento/fisiologia , Dança/fisiologia , Exercício Físico/fisiologia , Hormônios/sangue , Força Muscular/fisiologia , Equilíbrio Postural/fisiologia , Ioga , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Composição Corporal/fisiologia , Sulfato de Desidroepiandrosterona/sangue , Estrogênios/sangue , Feminino , Seguimentos , Nível de Saúde , Hormônio do Crescimento Humano/sangue , Humanos , Avaliação de Resultados em Cuidados de Saúde , Amplitude de Movimento Articular/fisiologia , República da Coreia , Saúde da Mulher
6.
Nutrients ; 11(11)2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31694190

RESUMO

BACKGROUND: Flavonoids potentially exert anti-cancer effects, as suggested by their chemical structures and supported by animal studies. In observational studies, however, the association between flavonoids and breast cancer, and potential underlying mechanisms, remain unclear. OBJECTIVE: To examine the relationship between flavonoid intake and sex hormone levels using timed blood samples in follicular and luteal phases in the Nurses' Health Study II among premenopausal women. METHODS: Plasma concentrations of estrogens, androgens, progesterone, dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), prolactin, and sex hormone-binding globulin (SHBG) were measured in samples collected between 1996 and 1999. Average flavonoid were calculated from semiquantitative food frequency questionnaires collected in 1995 and 1999. We used generalized linear models to calculate geometric mean hormone concentrations across categories of the intake of flavonoids and the subclasses. RESULTS: Total flavonoid intake generally was not associated with the hormones of interest. The only significant association was with DHEAS (p-trend = 0.02), which was 11.1% (95% confidence interval (CI): -18.6%, -3.0%) lower comparing the highest vs. lowest quartile of flavonoid intake. In subclass analyses, the highest (vs. lowest) quartile of flavan-3-ol intake was associated with significantly lower DHEAS concentrations (-11.3% with 95% CI: -18.3%, -3.7%, p-trend = 0.01), and anthocyanin intake was associated with a significant inverse trend for DHEA (-18.0% with 95% CI: -27.9%, -6.7%, p-trend = 0.003). CONCLUSION: Flavonoid intake in this population had limited impact on most plasma sex hormones in premenopausal women. Anthocyanins and flavan-3-ols were associated with lower levels of DHEA and DHEAS.


Assuntos
Ingestão de Alimentos/fisiologia , Flavonoides/análise , Hormônios Esteroides Gonadais/sangue , Pré-Menopausa/sangue , Prolactina/sangue , Globulina de Ligação a Hormônio Sexual/análise , Adulto , Androgênios/sangue , Antocianinas/análise , Desidroepiandrosterona/sangue , Sulfato de Desidroepiandrosterona/sangue , Inquéritos sobre Dietas , Estrogênios/sangue , Feminino , Inquéritos Epidemiológicos , Humanos , Modelos Lineares , Pessoa de Meia-Idade
7.
Artigo em Inglês | MEDLINE | ID: mdl-31703451

RESUMO

: Objective/introduction: The dynamics of ovarian hormone fluctuations during the luteal phase of the menstruation cycle were previously suggested to contribute to the development of premenstrual dysphoric disorder (PMDD) symptoms, but adequate empirical evidence has not been obtained from hormone concentration studies. We prospectively evaluated estrogen and progesterone levels in the early luteal (EL) and late luteal (LL) phases in women with PMDD and the association of these levels with PMDD symptom severity. Methods: 63 women with PMDD and 53 controls without such severe symptoms were evaluated for the estrogen and progesterone levels, and PMDD severity in the EL and LL phases. Results: The results demonstrated that the women with PMDD had a lower EL-phase estrogen level than the controls. Covariant analysis demonstrated that the interaction term between EL-phase estrogen and EL-phase progesterone level was associated with PMDD severity. Among women with lower EL estrogen levels, higher EL-phase progesterone was observed among the women with PMDD versus controls. These results suggest that low EL-phase estrogen level could moderate the provoking effect of EL progesterone in women with PMDD. Overall, these data suggest a possible role of estrogen and progesterone in the development of PMDD symptoms.


Assuntos
Estrogênios/sangue , Fase Luteal/sangue , Transtorno Disfórico Pré-Menstrual/sangue , Progesterona/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Ciclo Menstrual , Síndrome Pré-Menstrual , Adulto Jovem
8.
Medicine (Baltimore) ; 98(47): e18171, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31764859

RESUMO

RATIONALE: Sclerosing stromal tumor (SST) of the ovary is rare. We describe the first case of ovarian SST with estrogen excess with both clinical and serological evidence in a postmenopausal woman. PATIENT CONCERNS: A 70-year-old female who referred menopause 14 years ago was admitted with postmenopausal bleeding for 3 months. Ultrasonography revealed thickened endometrium of 6 mm and no adnexal masses. An elevated serum estradiol level of 49.78 ng/L was revealed in laboratory examination with normal ranges less than 27.25 ng/L in postmenopausal women. DIAGNOSES: The final histology diagnosis is SST of left ovary and endometrial hyperplasia with polyps. INTERVENTIONS: Laparoscopic hysterectomy and bilateral salpingo-oophorectomy were performed and a solid tumor with a diameter of 3 cm × 2 cm from the left ovary was found intraoperatively. OUTCOMES: Three days after removal of the tumor, the serum estrogen level was decreased to normal which indicated the estrogen activity of the tumor. LESSONS: To the best of our knowledge, it is the first reported case of ovarian SST with estrogen excess with both clinical and serological evidence. The present case illustrates the necessity to consider the rare possibility of ovarian SST as a cause for estrogen excess leading to postmenopausal bleeding. Hormonal evaluation (estrogens, androgens) should be considered in women with postmenopausal bleeding regardless of imaging examination.


Assuntos
Estrogênios/sangue , Neoplasias Ovarianas/sangue , Tumores do Estroma Gonadal e dos Cordões Sexuais/sangue , Idoso , Feminino , Humanos , Pós-Menopausa
9.
PLoS One ; 14(10): e0224504, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31652293

RESUMO

The purpose of this study was to investigate the associations and explore the relationships between hormonal factors (serum estrogen, estrogen receptors and ovariohysterectomy) and other clinical/histological prognostic factors and their impact on outcome in dogs with mammary carcinomas. Data from two separate prospective studies on dogs with spontaneous mammary carcinomas were used for this research. All dogs underwent standardized diagnostic testing, staging, surgery and follow-up examinations. Serum estrogen was analyzed by competitive enzyme immunoassay or radioimmunoassay, and tumor estrogen receptor (ER) expression was analyzed by immunohistochemistry. A total of 159 dogs were included; 130 were spayed and 29 remained. High serum estrogen was associated with an overall longer time to metastasis (p = 0.021). When stratifying based on spay group, the effect was only significant in spayed dogs, (p = 0.019). Positive tumor ER expression was also associated with a longer time to metastasis (p = 0.025), but similar to above, only in dogs that were spayed (p = 0.049). Further subgroup analysis revealed that high serum estrogen was significantly associated with improved survival in dogs with ER positive tumors, but only in spayed dogs (p = 0.0052). Interestingly, the effect of spaying was the opposite in dogs with ER negative tumors; here, intact dogs with high serum estrogen but ER negative tumors had a significantly longer time to metastasis (p = 0.036). Low serum estrogen was associated with increased risk for the development of non-mammary tumors in the post-operative period (p = 0.012). These results highlight the dual effect of estrogen in cancer: Estrogen acts as a pro-carcinogen in ER positive mammary tumors, but a may have a protective effect in ER negative tumors, potentially via non-receptor mechanisms. The latter is supported by the decreased risk for non-mammary tumors in dogs with high serum estrogen, and explains the increased incidence of certain non-mammary tumors in in dogs spayed at an early age.


Assuntos
Estrogênios/sangue , Neoplasias Mamárias Experimentais/sangue , Neoplasias Mamárias Experimentais/patologia , Animais , Cães , Feminino , Ovariectomia , Receptores Estrogênicos/sangue
10.
Cancer Causes Control ; 30(11): 1201-1211, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31542834

RESUMO

PURPOSE: Menopausal hormone therapy (MHT) use induces alterations in circulating estrogens/estrogen metabolites, which may contribute to the altered risk of reproductive tract cancers among current users. Thus, the current study assessed associations between circulating estrogens/estrogen metabolites and ovarian and endometrial cancer risk among MHT users. METHODS: We conducted a nested case-control study among postmenopausal women using MHT at baseline in the Women's Health Initiative Observational Study (179 ovarian cancers, 396 controls; 230 endometrial cancers, 253 controls). Multivariable logistic regression was utilized to estimate odds ratios and 95% confidence intervals overall and by subtype. RESULTS: Estrogen/estrogen metabolite levels were not associated with overall or serous ovarian cancer risk, examined separately. However, unconjugated estradiol was positively associated with non-serous ovarian cancer risk [quintile 5 vs. quintile 1: 3.01 (1.17-7.73); p-trend = 0.03; p-het < 0.01]. Endometrial cancer risk was unrelated to estrogen/estrogen metabolite levels among women who took combined estrogen/progestin therapy (EPT). CONCLUSIONS: These findings provide novel evidence that may support a heterogeneous hormonal etiology across ovarian cancer subtypes. Circulating estrogens did not influence endometrial cancer risk among women with EPT-induced high-estrogen levels. Larger studies are needed to delineate the relationship between ovarian/endometrial cancer subtypes and estrogen levels in the context of MHT use.


Assuntos
Neoplasias do Endométrio/sangue , Estradiol/sangue , Estrogênios/sangue , Terapia de Reposição Hormonal , Neoplasias Ovarianas/sangue , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Pós-Menopausa , Risco
11.
Reprod Domest Anim ; 54(11): 1470-1476, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31444980

RESUMO

The objective of this study was to examine the impact of a bovine respiratory disease complex (BRDC) vaccine with a temperature-sensitive modified live vaccine (MLV) infectious bovine rhinotracheitis (IBR) component on oestrous cycle parameters and the follicular pool. Twenty-four Holstein heifers (12.4 ± 0.5 months) previously calfhood vaccinated with an IBR MLV component were enrolled in two replicates (Spring; n = 10 and Fall; n = 14) and were blocked by pre-vaccination bovine viral diarrhoea (BVD) serum neutralizing (SN) titres. Upon enrolment, heifers were oestrous synchronized with sampling beginning at detected oestrus. At their second heat, heifers were vaccinated with a BRDC calfhood vaccine with a MLV (MLV; n = 12) or killed (K; n = 12) IBR component and sampled for two additional cycles. Serum samples for oestrogen (E2) and progesterone (P4) as well as ultrasound data of ovarian structures were collected every other day. Serum samples for anti-Müllerian hormone (AMH) were collected at oestrus and mid-cycle for each cycle, and serum for titres was collected prior to and following vaccination. Data were analysed with the PROC MIXED and GLM procedures of SAS. There was no difference in pre- or post-vaccination titres between MLV and K heifers (p > .5). Vaccination had no impact on P4 concentrations, P4 area under the curve, luteal tissue area, peak E2 production or oestrous cycle length (p > .05). Cycle number did impact AMH concentration (p < .05). In MLV heifers, AMH concentration was highest in cycle 1 (p < .05) while cycles 2 and 3 did not differ (p > .05). This was also true for the K heifers in the Fall replicate (p < .05). Within cycle 2, AMH concentrations were numerically lower between vaccine types (K = 308.22 ± 33.3 pg/ml, MLV = 181.13 ± 32.9 pg/ml; p > .05). Although no differences were seen in overall cycle parameters, differences in AMH concentrations may indicate a reduction of the follicular pool following vaccination and requires further investigation.


Assuntos
Hormônio Antimülleriano/sangue , Doenças dos Bovinos/prevenção & controle , Ciclo Estral/fisiologia , Rinotraqueíte Infecciosa Bovina/prevenção & controle , Animais , Bovinos , Estrogênios/sangue , Feminino , Rinotraqueíte Infecciosa Bovina/imunologia , Progesterona/sangue , Vacinação/efeitos adversos , Vacinação/veterinária , Vacinas Atenuadas , Vacinas Combinadas , Vacinas Virais/administração & dosagem
12.
J Ethnopharmacol ; 245: 112175, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31442621

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Marantodes pumilum (Blume) Kuntze has traditionally been used to firm the uterus after delivery, however scientific evidences behind this claim is still lacking. AIMS OF STUDY: To demonstrate Marantodes pumilum leaves aqueous extract (MPE) has an effect on uterine contraction after delivery and to elucidate the molecular mechanisms involved. METHODS: Day-1 post-delivery female rats were given MPE (100, 250 and 500 mg/kg/day) orally for seven consecutive days. A day after the last treatment (day-8), rats were sacrificed and uteri were harvested and subjected for ex-vivo contraction study using organ bath followed by protein expression and distribution study by Western blotting and immunohistochemistry techniques, respectively. The proteins of interest include calmodulin-CaM, myosin light chain kinase-MLCK, sarcoplasmic reticulum Ca2+-ATPase (SERCA), G-protein α and ß (Gα and Gß), inositol-triphosphate 3-kinase (IP3K), oxytocin receptor-OTR, prostaglandin (PGF)2α receptor-PGFR, muscarinic receptor-MAChR and estrogen receptor (ER) isoforms α and ß. Levels of estradiol and progesterone in serum were determined by enzyme-linked immunoassay (ELISA). RESULTS: Ex-vivo contraction study revealed the force of uterine contraction increased with increasing doses of MPE. In addition, expression of CaM, MLCK, SERCA, Gα, Gß, IP3K, OTR, PGF2α, MAChR, Erα and ERß in the uterus increased with increasing doses of MPE. Serum analysis indicate that estradiol levels decreased while progesterone levels remained low at day-8 post-partum in rats receiving 250 and 500 mg/kg/day MPE. CONCLUSIONS: These findings support the claims that MPE help to firm the uterus and pave the way for its use as a uterotonic agent after delivery.


Assuntos
Extratos Vegetais/farmacologia , Primulaceae , Contração Uterina/efeitos dos fármacos , Animais , Estradiol/sangue , Estrogênios/sangue , Feminino , Folhas de Planta , Período Pós-Parto/sangue , Período Pós-Parto/fisiologia , Progesterona/sangue , Ratos Sprague-Dawley , Receptores Estrogênicos/fisiologia , Útero/efeitos dos fármacos , Útero/fisiologia
13.
Reprod Biol ; 19(3): 245-254, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31383475

RESUMO

Granulosa Cells (GCs) are sensitive to excessive production of reactive oxygen species (ROS). Quercetin (QUR) is a free radical scavenger which can alleviate oxidative stress through nuclear factor (erythroid-derived 2)-like 2 (Nrf2)/antioxidant response element (ARE) pathway and thioredoxin (Trx) system. We aimed to explore the probable protective role of QUR on cultured human GCs treated with hydrogen peroxide (H2O2) as an inducer of oxidative stress. MTT assay was applied for evaluating the cell cytotoxicity of QUR and H2O2. The rate of apoptotic cells and intracellular ROS generation were determined by Annexin V-FITC/PI staining and 2'-7'-dichlorodihydrofluorescein diacetate fluorescent probes (DCFH-DA), respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis and western blot analysis were used to evaluate the gene and protein expression of Nrf2 and kelch-like ech-associated protein 1 (Keap1)1. The Nrf2 and Trx activities were measured by Enzyme-linked Immunosorbent Assay (ELISA). The results indicated that QUR pretreatment can decrease ROS production and apoptosis induced by H2O2. In addition, QUR increased Nrf2 gene and protein expression, as well as its nuclear translocation. Moreover, in QUR-treated group, a lower level of Keap1 protein was observed, which was not reported as significant. The results also indicated a significant correlation between the expression of Nrf2 and Keap1 in QUR-treated group. Further, QUR protected GCs from oxidative stress by increasing Trx gene expression and activity. This study suggests that QUR as a supplementary factor may protect GCs from oxidative stress in diseases related to this condition.


Assuntos
Células da Granulosa/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Quercetina/farmacologia , Tiorredoxinas/metabolismo , Adulto , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Gonadotropina Coriônica/administração & dosagem , Gonadotropina Coriônica/farmacologia , Estrogênios/sangue , Feminino , Fármacos para a Fertilidade Feminina/administração & dosagem , Fármacos para a Fertilidade Feminina/farmacologia , Hormônio Foliculoestimulante Humano/administração & dosagem , Hormônio Foliculoestimulante Humano/farmacologia , Hormônio Liberador de Gonadotropina/administração & dosagem , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/farmacologia , Humanos , Estresse Oxidativo/fisiologia , Espécies Reativas de Oxigênio , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Tiorredoxinas/genética , Adulto Jovem
14.
Biosci Trends ; 13(3): 284-285, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31327799

RESUMO

Threatened abortion is a common complication of pregnancy. Since the underlying mechanisms behind this condition are complicated, predicting and treating threatened abortion is a challenge for clinicians. Interestingly, a recent article in Bioscience Trends (Biosci Trends 2019; DOI: 10.5582/bst.2019.01111) revealed a higher, not lower, level of ꞵ-human chorionic gonadotropin (hCG) and estrogen during the first 6 weeks of pregnancy, suggesting a novel association between ꞵ-hCG, estrogen, and threatened abortion. Unfortunately, this study was limited by its small sample size, unconvincing trial design, and inadequate exploration of the underlying mechanisms. This low-quality evidence indicates that a higher level of ꞵ- hCG and estrogen is associated with threatened abortion. However, that work provided some new insights for further studies of threatened abortion.


Assuntos
Ameaça de Aborto/diagnóstico , Ameaça de Aborto/patologia , Aborto Espontâneo/sangue , Aborto Espontâneo/diagnóstico , Aborto Espontâneo/tratamento farmacológico , Aborto Espontâneo/patologia , Ameaça de Aborto/sangue , Ameaça de Aborto/tratamento farmacológico , Gonadotropina Coriônica/sangue , Estrogênios/sangue , Feminino , Humanos , Gravidez , Progesterona/sangue
15.
Int J Mol Sci ; 20(13)2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31261736

RESUMO

The pathogenesis of inflammatory bowel diseases (IBD) seems to be associated with alterations of immunoregulation. Several lines of evidence suggest that estrogens play a role in the modulation of immune responses and may be related to the etiology of IBD. The purpose of this work was to examine the involvement of G protein-coupled estrogen receptor (GPER), estrogen receptor α (ERα), estrogen receptor ß (ERß) and ERα spliced variants ERα36 and ERα46 in Crohn's disease (CD) and ulcerative colitis (UC). The studied group included 73 patients with IBD and 31 sex and age-related controls. No differences in serum levels of 17ß-estradiol nor of CYP1A1 and SULT1E1 enzymes involved in estrogen catabolism were stated. The expression pattern of estrogen receptors in tissue samples was quantified using real-time PCR and Western blotting. Statistically significant up-regulation of GPER and ERα in both CD and UC as well as down-regulation of ERß in CD patients was found. However, differences in the expression of estrogen receptors in CD and UC have been identified, depending on the sex and age of patients. In men, up-regulation of GPER, ERα and ERα46 expression was shown in CD and UC patients. In women under 50 years of age, GPER protein level increased in UC whereas ERß expression tended to decrease in CD and UC patients. In turn, in women over 50 the protein level of ERα increased in UC while ERß expression decreased in CD patients. Dysregulation of estrogen receptors in the intestinal mucosa of patients with CD and UC indicates that estrogen signaling may play a role in the local immune response and maintain epithelial homeostasis in a gender- and age-dependent manner.


Assuntos
Colite Ulcerativa/metabolismo , Doença de Crohn/metabolismo , Estrogênios/metabolismo , Receptores Estrogênicos/metabolismo , Transdução de Sinais , Fatores Etários , Idoso , Colite Ulcerativa/patologia , Doença de Crohn/patologia , Estradiol/sangue , Estradiol/metabolismo , Estrogênios/sangue , Feminino , Humanos , Mucosa Intestinal/metabolismo , Masculino , Pessoa de Meia-Idade , Receptores Estrogênicos/genética , Fatores Sexuais
16.
Life Sci ; 232: 116640, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31295470

RESUMO

INTRODUCTION AND AIM: Polycystic ovary syndrome is one of the most common causes of female infertility, affecting 5-10% of the population. Women with PCOS manifest hyperandrogenism, hyperinsulinemia, low-grade systemic inflammation, and polycystic ovaries. Unfortunately, current available medications are only symptomatic without relevant reported treatment. Therefore, a pressing need for alternative safe approaches is necessitated. To this end, the present study is designed to investigate therapeutic merits of the edible plant: Ocimum kilimandscharicum (Ok), in a letrozole PCOS rat model, and compare it to metformin. MATERIAL AND METHODS: PCOS rats were treated with Ok total extract and its different fractions at 100 mg/kg orally for 10 consecutive days. Moreover, phytochemical characterization was applied using HPLC/PDA/ESI-MS to identify different secondary metabolites in the bioactive fractions. KEY FINDINGS: Results revealed that the total extract (Ok) and ethyl acetate (EA) fraction improved insulin sensitivity and restored normal hormonal and lipid profiles as well as normal morphological structure of the reproductive system. Furthermore, elevation of SOD and reduction of VEGF levels in comparison with metformin were recorded. SIGNIFICANCE: These results suggest that Ok extract and EA fraction halt letrozole-induced reproductive dysfunctions and restore normal morphological and physiological functions in PCOS rats, even superior to metformin.


Assuntos
Inibidores da Aromatase/farmacologia , Hipoglicemiantes/farmacologia , Letrozol/farmacologia , Metformina/farmacologia , Ocimum/química , Ovário/efeitos dos fármacos , Ovário/fisiopatologia , Extratos Vegetais/uso terapêutico , Síndrome do Ovário Policístico/tratamento farmacológico , Idoso , Animais , Antioxidantes/metabolismo , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Citocinas/metabolismo , Modelos Animais de Doenças , Estrogênios/sangue , Estro , Feminino , Glicosídeos/metabolismo , Humanos , Hidroxibenzoatos/metabolismo , Insulina/sangue , Tamanho do Órgão/efeitos dos fármacos , Ovário/patologia , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/patologia , Síndrome do Ovário Policístico/fisiopatologia , Progesterona/sangue , Ratos , Ratos Wistar , Espectrometria de Massas por Ionização por Electrospray , Testosterona/sangue , Triglicerídeos/sangue , Útero/efeitos dos fármacos
17.
Biomed Res Int ; 2019: 6539294, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31240219

RESUMO

Chemotherapy leads to a loss of fertility and reproductive endocrine function, thereby increasing the risk of premature ovarian failure (POF). Studies have suggested that the transplantation of mesenchymal stem cells could inhibit apoptosis in ovarian granulosa cells and improve follicular development. In the present study, the effects of human umbilical cord mesenchymal stem cell (UCMSC) transplantation on ovarian function after ovarian damage caused by chemotherapy and the mechanism underlying these effects were investigated. POF model rats were obtained by the intraperitoneal injection of cyclophosphamide, and cultured UCMSCs were transplanted by tail vein injection. Serum estrogen, follicle-stimulating hormone, gonadotropin releasing hormone, and anti-Mullerian hormone levels were detected by ELISA. Folliculogenesis was evaluated by histopathological examination. The expression levels of nerve growth factor (NGF), high affinity nerve growth factor receptor (TrkA), follicle-stimulating hormone receptor (FSHR), and caspase-3 were evaluated by western blotting and RT-qPCR. The natural reproductive capacity was assessed by pregnant rate and numbers of embryos. The results indicated that UCMSC transplantation recovered disturbed hormone secretion and folliculogenesis in POF rats. NGF and TrkA levels increased, while FSHR and caspase-3 decreased. The pregnancy rate of POF rats was improved. Therefore, UCMSCs could reduce ovarian failure due to premature senescence caused by chemotherapy, and the NGF/TrkA signaling pathway was involved in the amelioration of POF.


Assuntos
Antineoplásicos/efeitos adversos , Transplante de Células-Tronco Mesenquimais/métodos , Fator de Crescimento Neural/metabolismo , Insuficiência Ovariana Primária/terapia , Cordão Umbilical/transplante , Animais , Hormônio Antimülleriano/sangue , Apoptose/efeitos dos fármacos , Caspase 3/sangue , Ciclofosfamida/efeitos adversos , Estrogênios/sangue , Feminino , Hormônio Foliculoestimulante/sangue , Hormônio Liberador de Gonadotropina/sangue , Humanos , Células-Tronco Mesenquimais , Fator de Crescimento Neural/sangue , Ovário/patologia , Gravidez , Insuficiência Ovariana Primária/induzido quimicamente , Ratos , Ratos Sprague-Dawley , Receptores do FSH/sangue
18.
Artigo em Chinês | MEDLINE | ID: mdl-31163520

RESUMO

Objective:To investigate relationship between the level of estrogen, calcium and phosphorus concentration in serum with benign paroxysmal positional vertigo(BPPV). Method:A total of 84 patients with idiopathic BPPV were enrolled in the experimental group, including 32 non-menopausal women, 24 menopausal women, and 28 males; 83 healthy people without vertigo and vestibular disease were selected as the control group consisted with 32 non-menopausal women, 24 menopausal women and 27 males. The levels of estradiol, serum calcium and serum inorganic phosphorus were measured in all participants. The difference of estrogen level, serum calcium and serum inorganic phosphorus concentration between the experimental group and the control group was analyzed by t test. Result:The total number, age distribution and gender composition of the experimental group and the control group were basically paired, and the age difference was not statistically significant (P=0.71). The overall estrogen level in the experimental group was lower than that in the control group (P<0.01). Among them, the female group's estrogen level, menopausal female estrogen level and male estrogen level in the experimental group were lower than the control group (P<0.01); there was no significant difference in serum calcium and serum inorganic phosphorus concentration between the experimental group and the control group (P=0.55, 0.11, respectively). Conclusion:The decrease of estrogen level may be a risk factor for idiopathic BPPV. The relationship between serum calcium and serum inorganic phosphorus concentration and BPPV needs further study.


Assuntos
Vertigem Posicional Paroxística Benigna , Cálcio , Estrogênios , Fósforo , Adulto , Vertigem Posicional Paroxística Benigna/sangue , Cálcio/sangue , Estrogênios/sangue , Feminino , Humanos , Masculino , Menopausa , Pessoa de Meia-Idade , Fósforo/sangue
20.
Pharmacogenomics ; 20(8): 571-580, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31190621

RESUMO

Aim: This study tested for associations between SLCO1B1 polymorphisms and circulating estrogen levels in women with breast cancer treated with letrozole or exemestane. Patients & methods: Postmenopausal women with hormone-receptor positive breast cancer were genotyped for SLCO1B1*5 (rs4149056) and rs10841753. Pretreatment and on-treatment plasma estrogens and aromatase inhibitor (AI) concentrations were measured. Regression analyses were performed to test for pharmacogenetic associations with estrogens and drug concentrations. Results: SLCO1B1*5 was associated with elevated pretreatment estrone sulfate and an increased risk of detectable estrone concentrations after 3 months of AI treatment. Conclusion: These findings suggest SLCO1B1 polymorphisms may have an effect on estrogenic response to AI treatment, and therefore may adversely impact the anticancer effectiveness of these agents.


Assuntos
Androstadienos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Letrozol/administração & dosagem , Transportador 1 de Ânion Orgânico Específico do Fígado/genética , Androstadienos/efeitos adversos , Inibidores da Aromatase/administração & dosagem , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Receptor alfa de Estrogênio/genética , Estrogênios/sangue , Feminino , Genótipo , Humanos , Letrozol/efeitos adversos , Pessoa de Meia-Idade , Farmacogenética , Polimorfismo Genético , Tamoxifeno/administração & dosagem
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