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1.
Zoolog Sci ; 38(5): 451-458, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34664920

RESUMO

Viviparous fish, including white-edged rockfish (Sebastes taczanowskii), accumulate substantial yolk mass in the oocytes; however, the details of the molecular mechanisms underlying yolk formation are not yet fully understood, especially concerning multiplicity in the yolk precursor vitellogenin (Vtg). The present study aimed to reveal the hepatic transcriptional profiles of multiple vtg gene transcripts (vtgAa, vtgAb, vtgC) during the reproductive cycle in captive female white-edged rockfish reared in an aquarium under natural photo-thermal conditions. The serum estradiol-17ß concentration and the hepatic transcript levels of all vtg subtypes increased with the progress of vitellogenesis; both levels decreased at the beginning of oocyte maturation and remained low during the gestation period. Considering the similarity in the transcriptional profiles of vtg subtypes between Sebastes and Oncorhynchus, along with the differences between Sebastes and Morone, it is suggested that the transcription patterns of multiple vtg genes relate to neither their reproductive modes (viviparity versus oviparity) nor to teleost phylogeny.


Assuntos
Fígado/metabolismo , Perciformes/fisiologia , Vitelogeninas/metabolismo , Animais , Estradiol/sangue , Feminino , Ovário/fisiologia , Transcriptoma , Vitelogênese , Vitelogeninas/genética
2.
Zoolog Sci ; 38(5): 459-465, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34664921

RESUMO

Vitellogenesis in oviparous vertebrates is a critical marker of the restart of seasonal reproductive activity. During this process of multihormonal regulation, females allocate a considerable amount of organic and mineral reserves to the synthesis of yolk, with changes in their plasma values. In this work, we determined plasma levels of various metabolites and steroid hormones throughout the reproductive cycle in females of Salvator merianae who developed vitellogenic and non-vitellogenic follicular cycles. We worked for two consecutive years with 20 adult females from the Experimental Hatchery of the Facultad de Agronomía y Zootecnia of the Universidad Nacional de Tucumán. Values of metabolites: glucose, triglycerides, cholesterol, calcium, phosphorus, albumin, total proteins, and hormones: estradiol, progesterone, and testosterone, were determined during the following stages of the annual cycle: hibernation, hibernation emergence, courtship-mating, oviposition, and incubation. Vitellogenic females showed significantly higher plasma levels of triglycerides, calcium, phosphorus, and albumin than non-vitellogenic females, mainly in the courtship-mating stage (advanced vitellogenesis). In contrast, annual cholesterol averages were lower in vitellogenic females. Glucose showed changes throughout the annual cycle regardless of the vitellogenic condition. Total proteins plasma levels had very few fluctuations during the cycle. Among the hormones studied, only testosterone showed differences related to vitellogenic condition, with higher levels in non-vitellogenic females during the entire reproductive cycle. The knowledge of these changes associated with vitellogenesis will improve zootechnical management and will allow optimizing the reproductive efficiency of Salvator lizards in captivity.


Assuntos
Lagartos/fisiologia , Vitelogênese/fisiologia , Animais , Colesterol/sangue , Estradiol/sangue , Feminino , Lagartos/metabolismo , Folículo Ovariano/fisiologia , Progesterona/sangue , Reprodução/fisiologia , Testosterona/sangue , Triglicerídeos/sangue
3.
Eur Rev Med Pharmacol Sci ; 25(19): 5889-5903, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34661247

RESUMO

OBJECTIVE: Evidence supports a sex disparity in clinical outcomes of COVID-19 patients, with men exhibiting higher mortality rates compared to women. We aimed to test the correlation between serum levels of sex hormones [total testosterone, estradiol (E2), estradiol to testosterone (E2/T) ratio, progesterone), prolactin and 25-hydroxyvitamin D [25(OH)D] and markers of inflammation, coagulation and sepsis at admission in hospitalized men with COVID-19. PATIENTS AND METHODS: We conducted an exploratory retrospective study including symptomatic men with confirmed SARS-CoV-2 infection who were consecutively admitted to our Institution between April 1 and May 31, 2020. RESULTS: Patients were divided into survivors (n=20) and non-survivors (n=39). As compared to survivors, non-survivors showed significantly higher median neutrophil-to-lymphocyte ratio (NLR) values, D-dimer and procalcitonin (PCT) levels, along with significantly lower median 25(OH)D levels and total testosterone levels. Non-survivors exhibited significantly higher median values of E2/T ratio (a marker of aromatase activity). Spearman's correlation analysis revealed that total testosterone levels were significantly and inversely correlated with NLR, high-sensitivity C-reactive protein (hsCRP), interleukin-6, D-dimer and PCT. Conversely, E2/T ratio values were significantly and positively correlated with the aforementioned markers and with white blood cell (WBC) count. In a multivariate analysis performed by a logistic regression model after adjusting for major confounders (age, body mass index, hypertension and cardiovascular disease, diabetes mellitus and malignancy), total testosterone levels were significantly and inversely associated with risk of COVID-19-related in-hospital mortality. CONCLUSIONS: Low total testosterone levels and elevated E2/T ratio values at admission are associated with hyperinflammatory state in hospitalized men with COVID-19. Low total testosterone levels at admission represent an independent risk factor for in-hospital mortality in such patients. Therefore, total testosterone and E2/T ratio may serve as prognostic markers of disease severity in this population.


Assuntos
COVID-19/sangue , COVID-19/mortalidade , Estradiol/sangue , Inflamação/sangue , Inflamação/etiologia , Testosterona/sangue , Vitamina D/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Mortalidade Hospitalar , Hospitalização , Humanos , Contagem de Leucócitos , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Pró-Calcitonina/sangue , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Análise de Sobrevida , Vitamina D/sangue
4.
Sci Rep ; 11(1): 17743, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493761

RESUMO

Androgens have been implicated in autism pathophysiology as recently, prenatal exposure to elevated androgens has been proposed as risk factor. However, published data on postnatal sex hormone levels in autistic children are controversial and the source of prenatal androgen exposure in autism remains unknown. Therefore, this study investigated postnatal sex hormone levels and dehydroepiandrosterone (DHEA) to shed light on a potential role for the adrenal gland in autism pathophysiology. A case-control study investigating estradiol (E2), DHEA, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels was conducted with 31 Saudi males with autism and 28 healthy, age-matched boys plasma. Moreover, correlation analysis with measured hormones and previously measured total testosterone (TT) and free testosterone (FT) in the same group of autism was conducted. DHEA was significantly higher (p < 0.05) in the autism group compared to controls. DHEA positively correlated with previously measured TT (r = + 0.79, p < 0.001) and FT (r = + 0.72, p < 0.001) levels in the same autism group. FSH levels were also significantly higher in the autism group than in the control group (p < 0.01). To the best of our knowledge, this is the first study to report a strong positive correlation between TT, FT and DHEA, suggesting an adrenal source for elevated androgen levels.


Assuntos
Glândulas Suprarrenais/fisiopatologia , Transtorno Autístico/fisiopatologia , Antropometria , Transtorno Autístico/sangue , Estudos de Casos e Controles , Sulfato de Desidroepiandrosterona/sangue , Estradiol/sangue , Hormônio Foliculoestimulante/sangue , Humanos , Hormônio Luteinizante/sangue , Masculino , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangue
5.
Eur J Endocrinol ; 185(4): 539-552, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34342596

RESUMO

Objective: Sex steroid hormones like estrogens have a key role in the regulation of energy homeostasis and metabolism. In transwomen, gender-affirming hormone therapy like estradiol (in combination with antiandrogenic compounds) could affect metabolism as well. Given that the underlying pathophysiological mechanisms are not fully understood, this study assessed circulating estradiol-driven microRNAs (miRs) in transwomen and their regulation of genes involved in metabolism in mice. Methods: Following plasma miR-sequencing (seq) in a transwomen discovery (n = 20) and validation cohort (n = 30), we identified miR-224 and miR-452. Subsequent systemic silencing of these miRs in male C57Bl/6 J mice (n = 10) was followed by RNA-seq-based gene expression analysis of brown and white adipose tissue in conjunction with mechanistic studies in cultured adipocytes. Results: Estradiol in transwomen lowered plasma miR-224 and -452 carried in extracellular vesicles (EVs) while their systemic silencing in mice and cultured adipocytes increased lipogenesis (white adipose) but reduced glucose uptake and mitochondrial respiration (brown adipose). In white and brown adipose tissue, differentially expressed (miR target) genes are associated with lipogenesis (white adipose) and mitochondrial respiration and glucose uptake (brown adipose). Conclusion: This study identified an estradiol-drive post-transcriptional network that could potentially offer a mechanistic understanding of metabolism following gender-affirming estradiol therapy.


Assuntos
Micropartículas Derivadas de Células/genética , Estradiol/fisiologia , MicroRNAs/genética , Transexualidade , Adipócitos/efeitos dos fármacos , Adipócitos/fisiologia , Adipogenia/efeitos dos fármacos , Adipogenia/genética , Adulto , Animais , Micropartículas Derivadas de Células/efeitos dos fármacos , Micropartículas Derivadas de Células/metabolismo , Estudos de Coortes , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/genética , Estradiol/sangue , Estradiol/farmacologia , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Homeostase/efeitos dos fármacos , Terapia de Reposição Hormonal , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Interferência de RNA/efeitos dos fármacos , Pessoas Transgênero , Transexualidade/genética , Transexualidade/metabolismo , Adulto Jovem
6.
Medicine (Baltimore) ; 100(29): e26577, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34398012

RESUMO

ABSTRACT: Estradiol regulates spermatogenesis partly via estrogen receptor-alpha (ESRα). This study aimed to analyze the associations of serum estradiol level, serum ESRα level, and ESRα gene polymorphisms with sperm quality.This retrospective study included infertile men attending the Reproductive Center, Affiliated Hospital of Youjiang Medical University for Nationalities, and a control group without a history of fertility (October, 2016 to March, 2017). Data regarding sperm quality, serum levels of estradiol and ESRα, and rs2234693C/T genotype were extracted from the medical records. Pearson/Spearman correlations (as appropriate) between estradiol level, ESRα level, and sperm quality parameters were evaluated.The analysis included 215 men with infertility and 83 healthy controls. The infertile group had higher serum levels of estradiol (147.57 ±â€Š35.3 vs 129.62 ±â€Š49.11 pg/mL, P < .05) and ESRα (3.02 ±â€Š2.62 vs 1.33 ±â€Š0.56 pg/mL, P < .05) than the control group. For the infertile group, serum estradiol level was negatively correlated with sperm concentration, percentage of progressively motile sperm, and percentage of sperm with normal morphology (r = 0.309, 0.211, and 0.246, respectively; all P < .05). Serum estradiol and ESRα levels were lower in infertile men with normozoospermia than in those with azoospermia, oligozoospermia, mild azoospermia, or malformed spermatozoa (all P < .05). Sperm concentration, percentage of progressively motile sperm, serum ESRα level, and serum estradiol level did not differ significantly among the rs2234693 CC, CT, and TT genotypes.Elevated serum levels of estradiol and possibly ESRα might have a negative impact on sperm quality and fertility, whereas single nucleotide polymorphisms at rs2234693 of the ESRα gene had little or no effect.


Assuntos
Estradiol/análise , Receptor alfa de Estrogênio/análise , Infertilidade Masculina/sangue , Adulto , China , Estradiol/sangue , Receptor alfa de Estrogênio/sangue , Humanos , Infertilidade Masculina/genética , Masculino , Polimorfismo Genético/genética , Serviços de Saúde Reprodutiva/organização & administração , Serviços de Saúde Reprodutiva/estatística & dados numéricos , Estudos Retrospectivos , Análise do Sêmen/métodos , Contagem de Espermatozoides/métodos , Estatísticas não Paramétricas
7.
Emerg Microbes Infect ; 10(1): 1807-1818, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34402750

RESUMO

Male sex was repeatedly identified as a risk factor for death and intensive care admission. However, it is yet unclear whether sex hormones are associated with disease severity in COVID-19 patients. In this study, we analysed sex hormone levels (estradiol and testosterone) of male and female COVID-19 patients (n = 50) admitted to an intensive care unit (ICU) in comparison to control non-COVID-19 patients at the ICU (n = 42), non-COVID-19 patients with the most prevalent comorbidity (coronary heart diseases) present within the COVID-19 cohort (n = 39) and healthy individuals (n = 50). We detected significantly elevated estradiol levels in critically ill male COVID-19 patients compared to all control cohorts. Testosterone levels were significantly reduced in critically ill male COVID-19 patients compared to control cohorts. No statistically significant differences in sex hormone levels were detected in critically ill female COVID-19 patients, albeit similar trends towards elevated estradiol levels were observed. Linear regression analysis revealed that among a broad range of cytokines and chemokines analysed, IFN-γ levels are positively associated with estradiol levels in male and female COVID-19 patients. Furthermore, male COVID-19 patients with elevated estradiol levels were more likely to receive ECMO treatment. Thus, we herein identified that disturbance of sex hormone metabolism might present a hallmark in critically ill male COVID-19 patients.


Assuntos
COVID-19/mortalidade , COVID-19/patologia , Estradiol/sangue , Testosterona/sangue , Idoso , Idoso de 80 Anos ou mais , COVID-19/sangue , Cuidados Críticos , Estado Terminal , Oxigenação por Membrana Extracorpórea , Feminino , Humanos , Hipogonadismo/patologia , Unidades de Terapia Intensiva , Interferon gama/sangue , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Distribuição por Sexo
8.
Medicine (Baltimore) ; 100(34): e27072, 2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34449505

RESUMO

ABSTRACT: In patients with coronavirus disease 2019 (COVID-19), men are more severely affected than women. Multiple studies suggest that androgens might play a role in this difference in disease severity. Our objective was to assess the association between sex hormone levels and mortality in patients with severe COVID-19.We selected patients from the Amsterdam University Medical Centers COVID-19 Biobank, in which patients admitted to hospital in March and April 2020, with reverse transcription-polymerase chain reaction proven severe acute respiratory syndrome-coronavirus-2 infection, were prospectively included. Specifically, we included postmenopausal women (>55 years) and age-matched men, with a mortality of 50% in each group. Residual plasma samples were used to measure testosterone, estradiol, sex hormone binding globulin (SHBG), and albumin. We investigated the association of the levels of these hormones with mortality in men and women.We included 16 women and 24 men in March and April 2020 of whom 7 (44%) and 13 (54%), respectively, died. Median age was 69 years (interquartile range [IQR] 64-75). In men, both total and free testosterone was significantly lower in deceased patients (median testosterone 0.8 nmol/L [IQR 0.4-1.9] in deceased patients vs 3.2 nmol/L [IQR 2.1-7.5] in survivors; P < .001, and median free testosterone 33.2 pmol/L [IQR 15.3-52.2] in deceased patients vs 90.3 pmol/L [IQR 49.1-209.7] in survivors; P = .002). SHBG levels were significantly lower in both men and women who died (18.5 nmol/L [IQR 11.3-24.3] in deceased patients vs 34.0 nmol/L [IQR 25.0-48.0] in survivors; P < .001). No difference in estradiol levels was found between deceased and surviving patients.Low SHBG levels were associated with mortality rate in patients with COVID-19, and low total and free testosterone levels were associated with mortality in men. The role of testosterone and SHBG and potential of hormone replacement therapy needs further exploration in COVID-19.


Assuntos
COVID-19/sangue , COVID-19/epidemiologia , Hormônios Esteroides Gonadais/análise , Idoso , Albuminas/análise , COVID-19/mortalidade , Comorbidade , Grupos de Populações Continentais , Estradiol/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangue
9.
Am J Physiol Regul Integr Comp Physiol ; 321(3): R454-R468, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34346723

RESUMO

We evaluated maternal pregnancy adaptations and their relationships with circulating hormones in women who conceived with or without in vitro fertilization (IVF). Pregnancies were grouped by corpus luteum (CL) number: 1 CL with physiological plasma relaxin concentration (PRLN; spontaneous pregnancies); 0 CL without circulating RLN (programmed cycles); >1 CL with elevated PRLN (ovarian stimulation). Major findings were that declines in plasma osmolality (Posm) and plasma sodium concentration ([Formula: see text]) were comparable in the 1 CL and 0 CL cohorts, correlated with plasma estradiol and progesterone concentrations but not PRLN; gestational declines in plasma uric acid (UA) concentration (PUA) were attenuated after IVF, especially programmed cycles, partly because of subdued increases of renal UA clearance; and PRLN and cardiac output (CO) were inversely correlated when plasma estradiol concentration was below ∼2.5 ng/mL but positively correlated above ∼2.5 ng/mL. Unexpectedly, PRLN and plasma sFLT1 (PsFLT1) were directly correlated. Although PsFLT1 and CO were not significantly associated, CO was positively correlated with plasma placental growth factor (PLGF) concentration after the first trimester, particularly in women who conceived with 0 CL. Major conclusions are that 1) circulating RLN was unnecessary for gestational falls in Posm and [Formula: see text]; 2) PRLN and CO were inversely correlated during early gestation, suggesting that PRLN in the lower range may have contributed to systemic vasodilation, whereas at higher PRLN RLN influence became self-limiting; 3) evidence for cooperativity between RLN and estradiol on gestational changes in CO was observed; and 4) after the first trimester in women who conceived without a CL, plasma PLGF concentration was associated with recovery of CO, which was impaired during the first trimester in this cohort.


Assuntos
Fertilização In Vitro , Hormônios Gonadais/sangue , Hemodinâmica , Infertilidade/terapia , Adaptação Fisiológica , Adulto , Biomarcadores/sangue , Débito Cardíaco , Estradiol/sangue , Feminino , Humanos , Infertilidade/sangue , Infertilidade/fisiopatologia , Pessoa de Meia-Idade , Concentração Osmolar , Fator de Crescimento Placentário/sangue , Gravidez , Primeiro Trimestre da Gravidez/sangue , Relaxina/sangue , Sódio/sangue , Ácido Úrico/sangue , Vasodilatação , Adulto Jovem
10.
Artigo em Inglês | MEDLINE | ID: mdl-34224962

RESUMO

Monitoring estrogen levels, especially estradiol (E2), is amongst others important for determining menopausal status and guidance of breast cancer treatment. We validated a serum E2 and estrone (E1) liquid chromatography tandem-mass spectrometry assay (LC-MS/MS) suitable for quantitation in human subjects. In addition, we compared our method with an E2 immunoassay (IA) and established preliminary reference values. Validation parameters were within the predetermined acceptance criteria. Assay linearity ranges were 4-1500 pmol/L for E1 and 4-2500 pmol/L for E2. Imprecision ranged from 7.4 to 9.6%. The lower limit of quantitation for E2 (8.0 pmol/L) was 11.4 times lower than the IA. The method comparison revealed differences in E2 quantitation up to 155% between both methods. The method allowed quantitation of E1 in all healthy volunteers, while E2 could not be detected in 95% versus 40% of the post-menopausal women using IA and LC-MS/MS, respectively. Male, pre-, peri- and postmenopausal female reference values were estimated. An LC-MS/MS based method combining E1 and E2 analysis was validated with superior E2 analytical sensitivity when compared to the IA.


Assuntos
Cromatografia Líquida/métodos , Estradiol/sangue , Estrona/sangue , Imunoensaio/métodos , Espectrometria de Massas em Tandem/métodos , Adolescente , Adulto , Feminino , Humanos , Limite de Detecção , Modelos Lineares , Masculino , Menopausa , Pessoa de Meia-Idade , Valores de Referência , Reprodutibilidade dos Testes , Adulto Jovem
11.
Taiwan J Obstet Gynecol ; 60(4): 739-744, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34247817

RESUMO

OBJECTIVE: To evaluate the value of using both HMG and recombinant FSH (r-FSH) in the GnRH antagonist protocol for women with high AMH. MATERIALS AND METHODS: This retrospective, single-center cohort study was conducted from January 2013 to December 2018. Of 277 GnRH antagonist IVF/ICSI cycles in women with anti-Mullerian hormone (AMH) ≥5 µg/L, 170 cycles receiving the combination of r-FSH and HMG (77 with HMG added at the beginning of the GnRH antagonist cycle and 93 with HMG added after GnRH antagonist administration) and 107 cycles receiving r-FSH alone were analyzed. The dynamic hormone profiles and embryonic and clinical outcomes of the patients were evaluated. RESULTS: We observed significantly lower serum LH levels in the r-FSH + HMG groups during ovarian stimulation. The serum estradiol and progesterone levels were lower in the r-FSH + HMG groups on the trigger day. Nevertheless, there were no significant differences with respect to the number of oocytes retrieved, maturation, fertilization, blastocyst formation rate or ovarian hyperstimulation syndrome (OHSS). The implantation and live birth rates were increased in the r-FSH + HMG groups compared with the r-FSH alone group, with no statistical significance. CONCLUSIONS: HMG for LH supplementation in the GnRH antagonist protocol for patients with high AMH is not significantly superior to r-FSH alone in terms of ovarian response and pregnancy outcome. Nevertheless, HMG supplementation might be appropriate for women with an initially inadequate response to r-FSH or intracycle LH deficiency.


Assuntos
Hormônio Antimülleriano/sangue , Hormônio Foliculoestimulante/administração & dosagem , Hormônio Liberador de Gonadotropina/antagonistas & inibidores , Antagonistas de Hormônios/administração & dosagem , Menotropinas/administração & dosagem , Adulto , Coeficiente de Natalidade , Implantação do Embrião , Estradiol/sangue , Feminino , Fertilização In Vitro/métodos , Humanos , Hormônio Luteinizante/sangue , Indução da Ovulação/métodos , Gravidez , Progesterona/sangue , Estudos Retrospectivos , Injeções de Esperma Intracitoplásmicas/métodos , Resultado do Tratamento
12.
J Steroid Biochem Mol Biol ; 213: 105954, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34298098

RESUMO

BACKGROUND: The present study was conducted to investigate the therapeutic effects of a potent polyphenol, fisetin, on the letrozole-induced rat model of polycystic ovary syndrome (PCOS). METHODOLOGY: Twenty-four female Wistar rats (42 days old) were divided into four groups: control group (received carboxy methylcellulose (CMC 0.5 %)), PCOS group treated with letrozole (1 mg/kg), fisetin group received same dose of letrozole + fisetin (10 mg/kg), and metformin group received same dose of letrozole + metformin (300 mg/kg). At the end of the experiment, biochemical (glucose, lipid profile) and hormonal (insulin, testosterone, estradiol, and progesterone) parameters were analyzed. Histological examinations of ovaries were also conducted by hematoxylin and eosin (H&E) staining. Real-time polymerase chain reaction (PCR) and western blotting were carried out for cytochrome P450 17A1 (CYP17A1), sirtuin-1 (SIRT1), and 5' AMP-activated protein kinase (AMPK) gene expression in the ovaries. Furthermore, enzymatic activities of antioxidants including catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the ovaries were analyzed by colorimetric method. RESULTS: Letrozole administration resulted in a remarkable abnormality in biochemical and hormonal parameters. Fisetin normalized levels of glucose, lipid profile, homeostatic model assessment for insulin resistance (HOMA-IR), testosterone, estradiol, and progesterone. Moreover, fisetin increased expression levels of SIRT1 and AMPK, and decreased expression level of CYP17A1 in the ovaries. Additionally, fisetin showed protective effect by enhancing antioxidant activities of CAT, SOD, and GPx depleted secondary to induction of PCOS. Fisetin effects were comparable to metformin, as the standard drug used for treatment of PCOS. CONCLUSION: Our results showed that, fisetin treatment caused significant alleviating effects by restoring PCOS-induced alterations in the key genes involved in energy homeostasis and antioxidant enzymes, suggesting that it may have a key role in combating with PCOS.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Flavonóis/farmacologia , Letrozol/antagonistas & inibidores , Ovário/efeitos dos fármacos , Síndrome do Ovário Policístico/tratamento farmacológico , Proteínas Quinases Ativadas por AMP/sangue , Proteínas Quinases Ativadas por AMP/genética , Animais , Glicemia/metabolismo , Carboximetilcelulose Sódica/administração & dosagem , Catalase/sangue , Catalase/genética , Modelos Animais de Doenças , Estradiol/sangue , Feminino , Expressão Gênica , Glutationa Peroxidase/sangue , Glutationa Peroxidase/genética , Humanos , Insulina/sangue , Letrozol/toxicidade , Metformina/farmacologia , Ovário/metabolismo , Ovário/patologia , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/patologia , Progesterona/sangue , Ratos , Ratos Wistar , Sirtuína 1/sangue , Sirtuína 1/genética , Esteroide 17-alfa-Hidroxilase/antagonistas & inibidores , Esteroide 17-alfa-Hidroxilase/sangue , Esteroide 17-alfa-Hidroxilase/genética , Superóxido Dismutase/sangue , Superóxido Dismutase/genética , Testosterona/sangue
13.
Am J Physiol Regul Integr Comp Physiol ; 321(2): R273-R278, 2021 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-34259042

RESUMO

Prior data suggest that, relative to the early follicular phase, women in the late follicular phase are protected against endothelial ischemia-reperfusion (I/R) injury when estradiol concentrations are highest. In addition, endothelial I/R injury is consistently observed in men with naturally low endogenous estradiol concentrations that are similar to those of women in the early follicular phase. Therefore, the purpose of this study was to determine whether the vasodeleterious effect of I/R injury differs between women in the early follicular phase of the menstrual cycle and age-matched men. We tested the hypothesis that I/R injury would attenuate endothelium-dependent vasodilation to the same extent in women and age-matched men with similar circulating estradiol concentrations. Endothelium-dependent vasodilation was assessed via brachial artery flow-mediated dilation (duplex ultrasound) in young healthy men (n = 22) and women (n = 12) before (pre-I/R) and immediately after (post-I/R) I/R injury, which was induced via 20 min of arm circulatory arrest followed by 20-min reperfusion. Serum estradiol concentrations did not differ between sexes (men 115.0 ± 33.9 pg·mL-1 vs. women 90.5 ± 40.8 pg·mL-1; P = 0.2). The magnitude by which I/R injury attenuated endothelium-dependent vasodilation did not differ between men (pre-I/R 5.4 ± 2.4% vs. post-I/R 3.0 ± 2.7%) and women (pre-I/R 6.1 ± 2.8% vs. post-I/R 3.7 ± 2.7%; P = 0.9). Our data demonstrate that I/R injury similarly reduces endothelial function in women in the early follicular phase of the menstrual cycle and age-matched men with similar estradiol concentrations.


Assuntos
Braço/irrigação sanguínea , Artéria Braquial/fisiopatologia , Endotélio Vascular/fisiopatologia , Estradiol/sangue , Fase Folicular/sangue , Traumatismo por Reperfusão/fisiopatologia , Vasodilatação , Adulto , Artéria Braquial/diagnóstico por imagem , Feminino , Humanos , Masculino , Traumatismo por Reperfusão/sangue , Traumatismo por Reperfusão/diagnóstico por imagem , Fatores Sexuais , Adulto Jovem
15.
Am J Physiol Lung Cell Mol Physiol ; 321(4): L764-L774, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34318685

RESUMO

Sex-dependent differences in immunity and coagulation play an active role in the outcome of community-acquired pneumonia (CAP). Contact phase proteins act at the crossroads between inflammation and coagulation thus representing a point of convergence in host defense against infection. Here, we measured the levels of factor XII (FXII), FXIIa-C1 esterase inhibitor (C1INH) complexes, and high-molecular-weight kininogen (HK) in plasma of patients with CAP and correlated them to clinical disease severity. Levels of FXIIa-C1INH/albumin ratio were elevated, irrespective of sex, in plasma of patients with CAP (n = 139) as compared with age-matched donors (n = 58). No simultaneous decrease in FXII levels, indicating its consumption, was observed. Stratification by sex revealed augmented FXII levels in plasma of women with CAP as compared with sex-matched donors yet no apparent differences in men. This sex-specific effect was, however, attributable to lower FXII levels in female donors relative to men donors. Plasma estradiol levels mirrored those for FXII. Levels of HK/albumin ratio were decreased in CAP plasma as compared with donors, however, after stratification by sex, this difference was only observed in women and was related to higher HK/albumin values in female donors as opposed to male donors. Finally, strong negative correlation between plasma levels of HK/albumin ratio and CAP severity, as assessed by CRB65 score, in males and females was observed. Our study identifies sex-dependent differences in plasma levels of the contact phase proteins in elderly subjects that may contribute to specific clinical outcomes in CAP between men and women.


Assuntos
Infecções Comunitárias Adquiridas/sangue , Proteína Inibidora do Complemento C1/análise , Fator XII/análise , Cininogênios/sangue , Pneumonia/sangue , Idoso , Infecções Comunitárias Adquiridas/patologia , Estradiol/sangue , Feminino , Humanos , Masculino , Pneumonia/patologia , Albumina Sérica/análise , Fatores Sexuais
16.
Int J Mol Sci ; 22(11)2021 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-34070921

RESUMO

Breast cancer is the most common malignancy in women with high mortality. Sensitive and specific methods for the detection, characterization and quantification of endogenous steroids in body fluids or tissues are needed for the diagnosis, treatment and prognosis of breast cancer and many other diseases. At present, non-invasive diagnostic methods are gaining more and more prominence, which enable a relatively fast and painless way of detecting many diseases. Metabolomics is a promising analytical method, the principle of which is the study and analysis of metabolites in biological material. It represents a comprehensive non-invasive diagnosis, which has a high potential for use in the diagnosis and prognosis of cancers, including breast cancer. This short review focuses on the targeted metabolomics of steroid hormones, which play an important role in the development and classification of breast cancer. The most commonly used diagnostic tool is the chromatographic method with mass spectrometry detection, which can simultaneously determine several steroid hormones and metabolites in one sample. This analytical procedure has a high potential in effective diagnosis of steroidogenesis disorders. Due to the association between steroidogenesis and breast cancer progression, steroid profiling is an important tool, as well as in monitoring disease progression, improving prognosis, and minimizing recurrence.


Assuntos
Androstenodiona/sangue , Neoplasias da Mama/diagnóstico , Desidroepiandrosterona/sangue , Di-Hidrotestosterona/sangue , Estradiol/sangue , Estrona/análogos & derivados , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/patologia , Estrona/sangue , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Imunoensaio , Redes e Vias Metabólicas , Metabolômica/instrumentação , Metabolômica/métodos , Recidiva , Espectrometria de Massas em Tandem
17.
Environ Toxicol Pharmacol ; 87: 103693, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34166789

RESUMO

Polybrominated diphenyl esters are emerging environmental contaminants with few toxicological data, being a concern for the scientific community. This study evaluated the effects of BDE-47 on the health of Oreochromis niloticus fish. The animals were exposed to three doses of BDE-47 (0, 0.253, 2.53, 25.3 ng g-1) every 10 days, for 80 days. The BDE-47 affected the hepatosomatic and gonadosomatic index in female and the condition factor by intermediate dose in both sexes. The levels of estradiol decreased and the T4 are increased, but the vitellogenin production was not modulated in male individuals. Changes in AChE, GST, LPO and histopathology were observed while the integrated biomarker response index suggests that the lowest dose of BDE-47 compromised the activity of antioxidant enzymes. The oral exposure to BDE-47 in environmental concentrations is toxic to O. niloticus and the use of multiple biomarkers is an attribution in ecotoxicology studies and biomonitoring programs.


Assuntos
Ciclídeos , Éteres Difenil Halogenados/toxicidade , Poluentes Químicos da Água/toxicidade , Acetilcolinesterase/metabolismo , Administração Oral , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Ciclídeos/sangue , Ciclídeos/metabolismo , Estradiol/sangue , Feminino , Glutationa Transferase/metabolismo , Gônadas/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Músculos/efeitos dos fármacos , Músculos/metabolismo , Tireotropina/sangue , Tiroxina/sangue , Vitelogeninas/sangue
18.
BMC Pregnancy Childbirth ; 21(1): 418, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34090383

RESUMO

BACKGROUND: Premature ovarian insufficiency (POI) is characterized by impairment of ovarian function on a continuum before the age of 40 years. POI is affected by multiple factors. Considering new insights from recent gut microbiome studies, this study aimed to investigate the relationship between gut microbial community structure and POI. METHODS: Subjects were recruited at the Shenzhen Maternity & Child Healthcare Hospital. Fecal microbial community profiles of healthy women (n = 18), women with POI (n = 35) were analyzed using 16S rRNA gene sequencing based on Illumina NovaSeq platform. RESULTS: Compared to the controls, the serum levels of FSH, LH, T and FSH/LH ratio significantly increased in women with POI, whereas E2 and AMH decreased significantly. Higher weighted UniFrac value was observed in POI women compared with healthy women. Phylum Firmicutes, genera Bulleidia and Faecalibacterium were more abundant in healthy women, while phylum Bacteroidetes, genera Butyricimonas, Dorea, Lachnobacterium and Sutterella enriched significantly in women with POI. Moreover, these alterations of the gut microbiome in women with POI were closely related to FSH, LH, E2, AMH level and FSH/LH ratio. CONCLUSIONS: Women with POI had altered microbial profiles in their gut microbiome, which were associated with serum hormones levels. These results will shed a new light on the pathogenesis and treatment for POI.


Assuntos
Microbioma Gastrointestinal , Insuficiência Ovariana Primária , Adulto , Estudos de Casos e Controles , Estradiol/sangue , Fezes/microbiologia , Feminino , Humanos , RNA Ribossômico 16S/análise , Adulto Jovem
19.
Elife ; 102021 06 07.
Artigo em Inglês | MEDLINE | ID: mdl-34096502

RESUMO

Traditionally, research unraveling seasonal neuroplasticity in songbirds has focused on the male song control system and testosterone. We longitudinally monitored the song behavior and neuroplasticity in male and female starlings during multiple photoperiods using Diffusion Tensor and Fixel-Based techniques. These exploratory data-driven whole-brain methods resulted in a population-based tractogram confirming microstructural sexual dimorphisms in the song control system. Furthermore, male brains showed hemispheric asymmetries in the pallium, whereas females had higher interhemispheric connectivity, which could not be attributed to brain size differences. Only females with large brains sing but differ from males in their song behavior by showing involvement of the hippocampus. Both sexes experienced multisensory neuroplasticity in the song control, auditory and visual system, and cerebellum, mainly during the photosensitive period. This period with low gonadal hormone levels might represent a 'sensitive window' during which different sensory and motor systems in the cerebrum and cerebellum can be seasonally re-shaped in both sexes.


Assuntos
Cerebelo/fisiologia , Cérebro/fisiologia , Plasticidade Neuronal , Estorninhos/fisiologia , Vocalização Animal , Animais , Percepção Auditiva , Cerebelo/diagnóstico por imagem , Cerebelo/metabolismo , Cérebro/diagnóstico por imagem , Cérebro/metabolismo , Imagem de Tensor de Difusão , Estradiol/sangue , Feminino , Masculino , Atividade Motora , Fotoperíodo , Estações do Ano , Caracteres Sexuais , Estorninhos/sangue , Testosterona/sangue , Percepção Visual
20.
J Clin Endocrinol Metab ; 106(10): 3007-3018, 2021 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-34097071

RESUMO

CONTEXT: Abnormalities in the hypothalamic-pituitary-adrenal (HPA) axis are frequent accompaniments of depression, and studies have documented the role of stress and stressful life events in the ontogeny of perimenopausal depressions (PMD). Because HPA axis function in women is further modulated both by aging and ovarian steroids, it is possible that a dysregulated HPA axis contributes to the increased risk of PMD. OBJECTIVE: We examined HPA axis function in perimenopausal women with and without depression using the combined dexamethasone-corticotropin-releasing hormone (Dex/CRH) test. METHODS: Dex/CRH tests were performed on 20 women with PMD and 20 women who were also perimenopausal but without current or past depression (control women). Main outcome measures were plasma levels of cortisol and adrenocorticotropin (ACTH) and 24-hour urinary free cortisol (UFC). Five women took chronic stable medications, otherwise all women were medically healthy, and both groups were comparable with respect to reproductive stage and age. Standardized symptom rating scales were administered to each woman prior to Dex/CRH testing. RESULTS: No group differences were present in either baseline or stimulated ACTH and cortisol secretion. Baseline plasma measures of estradiol, progesterone, and 24-hour UFC levels similarly did not differ in PMD and control women. CONCLUSION: Despite reports of increased stress responsiveness in PMD, we observed no abnormalities of HPA axis activity associated with PMD compared with women without depression. These findings suggest that PMD is not uniformly associated with HPA dysregulation and could reflect underlying pathophysiologic processes that are distinct from women with nonreproductive-related depressions.


Assuntos
Hormônio Adrenocorticotrópico/efeitos dos fármacos , Hormônio Liberador da Corticotropina/administração & dosagem , Depressão/fisiopatologia , Dexametasona/administração & dosagem , Hidrocortisona/metabolismo , Perimenopausa/efeitos dos fármacos , Hormônio Adrenocorticotrópico/sangue , Adulto , Estradiol/sangue , Feminino , Humanos , Sistema Hipotálamo-Hipofisário/fisiopatologia , Pessoa de Meia-Idade , Perimenopausa/metabolismo , Perimenopausa/psicologia , Sistema Hipófise-Suprarrenal/fisiopatologia , Progesterona/sangue
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