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1.
Endocrinology ; 163(1)2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34614143

RESUMO

AROMATASE is encoded by the CYP19A1 gene and is the cytochrome enzyme responsible for estrogen synthesis in vertebrates. In most mammals, a peak of CYP19A1 gene expression occurs in the fetal XX gonad when sexual differentiation is initiated. To elucidate the role of this peak, we produced 3 lines of TALEN genetically edited CYP19A1 knockout (KO) rabbits that were devoid of any estradiol production. All the KO XX rabbits developed as females with aberrantly small ovaries in adulthood, an almost empty reserve of primordial follicles, and very few large antrum follicles. Ovulation never occurred. Our histological, immunohistological, and transcriptomic analyses showed that the estradiol surge in the XX fetal rabbit gonad is not essential to its determination as an ovary, or for meiosis. However, it is mandatory for the high proliferation and differentiation of both somatic and germ cells, and consequently for establishment of the ovarian reserve.


Assuntos
Estrogênios/metabolismo , Ovário/embriologia , Ovário/fisiologia , Processos de Determinação Sexual/fisiologia , Animais , Hormônio Antimülleriano/metabolismo , Diferenciação Celular , Proliferação de Células , Família 19 do Citocromo P450/metabolismo , Estradiol/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Gônadas , Mutação INDEL , Folículo Ovariano/fisiologia , Ovulação , Fenótipo , Coelhos , Diferenciação Sexual/fisiologia , Testosterona/metabolismo
2.
Endocrinology ; 163(1)2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34864989

RESUMO

We have previously reported that hexamethylene bis-acetamide inducible protein 1 (HEXIM1) inhibits the activity of ligand-bound estrogen receptor α (ERα) and the androgen receptor (AR) by disrupting the interaction between these receptors and positive transcriptional elongation factor b (P-TEFb) and attenuating RNA polymerase II (RNAPII) phosphorylation at serine 2. Functional consequences of the inhibition of transcriptional activity of ERα and AR by HEXIM1 include the inhibition of ERα- and AR-dependent gene expression, respectively, and the resulting attenuation of breast cancer (BCa) and prostate cancer (PCa) cell proliferation and growth. In our present study, we determined that HEXIM1 inhibited AKR1C3 expression in BCa and PCa cells. AKR1C3, also known as 17ß-hydroxysteroid dehydrogenase (17ß-HSD) type 5, is a key enzyme involved in the synthesis of 17ß-estradiol (E2) and 5-dihydrotestosterone (DHT). Downregulation of AKR1C3 by HEXIM1 influenced E2 and DHT production, estrogen- and androgen-dependent gene expression, and cell proliferation. Our studies indicate that HEXIM1 has the unique ability to inhibit both the transcriptional activity of the ER and AR and the synthesis of the endogenous ligands of these receptors.


Assuntos
Di-Hidrotestosterona/metabolismo , Regulação para Baixo , Estradiol/metabolismo , Receptor alfa de Estrogênio/metabolismo , Regulação da Expressão Gênica , Proteínas de Ligação a RNA/biossíntese , Receptores Androgênicos/metabolismo , Fatores de Transcrição/biossíntese , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Estrogênios/metabolismo , Feminino , Humanos , Ligantes , Células MCF-7 , Masculino , Neoplasias da Próstata/metabolismo , RNA Interferente Pequeno/metabolismo
3.
Artigo em Inglês | MEDLINE | ID: mdl-34455080

RESUMO

Dmrt1 is an important transcriptional regulator that plays critical role in male gonadogenesis, testicular differentiation and development. In this study, Dmrt1 was cloned from blotched snakehead (Channa maculata), which is designated as CmDmrt1. CmDmrt1 encoded a putative protein with 293 amino acids and presented an extremely conserved DM domain. It was nearly expressed in the gonads, and the expression was more than 15 times higher in the testis than in the ovary. 1851 bp promoter sequence of CmDmrt1 was characterized and the methylation levels of the CpG sites were analyzed to detect sex-related differences. A significant negative correlation between CmDmrt1 expression and CpG methylation level of its promoter was found in the testis and ovary. During gonadal development, CmDmrt1 transcription displayed strong male-biased expression patterns, increased with the maturation of testis and reached the peak at 195 days after hatching (dah), which indicates a significant role of Dmrt1 in spermatogenesis. Steroid treatment could influence CmDmrt1 expression, and long-term 17ß-estradiol (E2) treatment could induce the male-to-female secondary sex reversal (SSR), which resulted in the differentiated testis transformed to ovary or ovotestis. Meanwhile, CmDmrt1 expression was down-regulated to fairly low level in the ovary of the SSR XY fish, which was similar to that in normal XX females ovary. Our research illustrates that Dmrt1 is linked to testis differentiation and spermatogenesis in blotched snakehead, providing information for functional studies on sex differentiation and gonadal development of C. maculata, and scientific basis for the production practice of all-male snakehead breeding.


Assuntos
Gônadas , Diferenciação Sexual , Animais , Estradiol/metabolismo , Estradiol/farmacologia , Feminino , Peixes/genética , Regulação da Expressão Gênica no Desenvolvimento , Gônadas/metabolismo , Masculino , Metilação , Diferenciação Sexual/genética , Testículo/metabolismo
4.
J Steroid Biochem Mol Biol ; 215: 106025, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34775032

RESUMO

Nowadays, 17ß-estradiol (E2) biodegradation pathway has still not been identified in bacteria. To bridge this gap, we have described a novel E2 degradation pathway in Rhodococcus sp. P14 in this study, which showed that estradiol could be first transferred to estrone (E1) and thereby further converted into 16-hydroxyestrone, and then transformed into opened estrogen D ring. In order to identify the genes, which may be responsible for the pathway, transcriptome analysis was performed during E2 degradation in strain P14. The results showed that the expression of a short-chain dehydrogenase (SDR) gene and a CYP123 gene in the same gene cluster could be induced significantly by E2. Based on gene analysis, this gene cluster was found to play an important role in transforming E2 to 16-hydroxyestrone. The function of CYP123 was unknown before this study, and was found to harbor the activity of 16-estrone hydratase. Moreover, the global response to E2 in strain P14 was also analyzed by transcriptome analysis. It was observed that various genes involved in the metabolism processes, like the TCA cycle, lipid and amino acid metabolism, as well as glycolysis showed a significant increase in mRNA levels in response to strain P14 that can use E2 as the single carbon source. Overall, this study provides us an in depth understanding of the E2 degradation mechanisms in bacteria and also sheds light about the ability of strain P14 to effectively use E2 as the major carbon source for promoting its growth.


Assuntos
Carbonil Redutase (NADPH)/genética , Sistema Enzimático do Citocromo P-450/genética , Estradiol/metabolismo , Regulação Bacteriana da Expressão Gênica , Rhodococcus/metabolismo , Transcriptoma , Biotransformação , Carbono/metabolismo , Carbonil Redutase (NADPH)/metabolismo , Ciclo do Ácido Cítrico/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Estrona/metabolismo , Ontologia Genética , Hidroxiestronas/metabolismo , Metabolismo dos Lipídeos/genética , Anotação de Sequência Molecular , Família Multigênica , Filogenia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Rhodococcus/classificação , Rhodococcus/genética
5.
Int J Mol Sci ; 22(24)2021 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-34948369

RESUMO

It has been reported that 17ß-estradiol (E2) can exert beneficial effects against the development of obesity, providing women with a healthier metabolic profile and conferring cardiovascular protection. However, a growing body of evidence questions this role in the context of obesity and diabetes. We focus on the adipose tissue-heart axis to address the question of whether E2 can have metabolically detrimental effects in an obese-diabetic rat model. Female Zucker Diabetic Fatty rats were used: LEAN, fa/+; SHAM, sham-operated fa/fa; OVA, ovariectomized fa/fa, and OVA+E2, ovariectomized and E2 treated fa/fa. The secretory expression profile, tissue expansion parameters and composition of visceral adipose tissue, as well as systemic and cardiac parameters related to insulin resistance, fibrosis, and inflammation were analyzed. Ovariectomy induced an attenuation of both diabetic condition and metabolic dysfunction of adipose tissue and cardiac muscle in fa/fa rats, suggesting that E2, in the context of diabetes and obesity, loses its cardioprotective role and could even contribute to greater metabolic alterations. Adipose tissue from OVA rats showed a healthier hyperplastic expansion pattern, which could help maintain tissue function, increase adiponectin expression, and decrease pro-inflammatory adipokines. These findings should be taken into account when considering hormone replacement therapy for obese-diabetic women.


Assuntos
Tecido Adiposo/metabolismo , Doenças Cardiovasculares/metabolismo , Complicações do Diabetes/metabolismo , Diabetes Mellitus/metabolismo , Estradiol/metabolismo , Obesidade/metabolismo , Tecido Adiposo/patologia , Animais , Doenças Cardiovasculares/patologia , Diabetes Mellitus/patologia , Estrogênios/metabolismo , Feminino , Obesidade/patologia , Ratos , Ratos Zucker
6.
Nutrients ; 13(12)2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34960109

RESUMO

Aging women experience hormonal changes, such as decreased estrogen and increased circulating androgen, due to natural or surgical menopause. These hormonal changes make postmenopausal women vulnerable to body composition changes, muscle loss, and abdominal obesity; with a sedentary lifestyle, these changes affect overall energy expenditure and basal metabolic rate. In addition, fat redistribution due to hormonal changes leads to changes in body shape. In particular, increased bone marrow-derived adipocytes due to estrogen loss contribute to increased visceral fat in postmenopausal women. Enhanced visceral fat lipolysis by adipose tissue lipoprotein lipase triggers the production of excessive free fatty acids, causing insulin resistance and metabolic diseases. Because genes involved in ß-oxidation are downregulated by estradiol loss, excess free fatty acids produced by lipolysis of visceral fat cannot be used appropriately as an energy source through ß-oxidation. Moreover, aged women show increased adipogenesis due to upregulated expression of genes related to fat accumulation. As a result, the catabolism of ATP production associated with ß-oxidation decreases, and metabolism associated with lipid synthesis increases. This review describes the changes in energy metabolism and lipid metabolic abnormalities that are the background of weight gain in postmenopausal women.


Assuntos
Composição Corporal , Metabolismo Energético , Metabolismo dos Lipídeos , Pós-Menopausa , Adipogenia , Idoso , Estradiol/metabolismo , Estrogênios/metabolismo , Ácidos Graxos não Esterificados/metabolismo , Feminino , Humanos , Resistência à Insulina , Gordura Intra-Abdominal/metabolismo , Transtornos do Metabolismo dos Lipídeos/metabolismo , Lipólise , Lipase Lipoproteica/metabolismo , Pessoa de Meia-Idade , Músculo Esquelético/metabolismo , Obesidade Abdominal/metabolismo , Oxirredução
7.
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
8.
J Agric Food Chem ; 69(40): 11847-11855, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34609142

RESUMO

Estrogen and its analogues are ubiquitous in agricultural environments, with large biological functions of oocyte development. Gap junction intercellular communications (GJICs) are the structural basis in cumulus-oocyte complexes (COCs) and regulate oocyte maturation and developmental material transport through a number of pathways. This study mainly determines the effect and potential mechanism of estrogen (17ß-estradiol) in regulating GJICs in porcine COCs. In our study, 17ß-estradiol increased porcine nuclear maturation in a time-dependent manner. The analysis revealed that 17ß-estradiol upregulated the autophagy in COCs during in vitro maturation. In contrast with the control, 17ß-estradiol decreased GJICs in a time-dependent manner between cumulus cells and oocytes, while it was consistent with the control group at 24 h. Carbenoxolone (CBX) blocks GJICs as a negative control group used in our system. Autophagy inhibitor autophinib decreased oocyte maturation, and the reduced nuclear maturation treated with autophinib was abolished by 17ß-estradiol. Besides, the upregulation effect of autophinib on GJICs and transzonal projections (TZPs) was decreased by 17ß-estradiol. 17ß-Estradiol could reduce serine 368 phosphorylation of connexin 43 (Cx43) protein by autophinib in porcine COCs. These results were dependent upon the MEK/ERK signaling pathway. Furthermore, 17ß-estradiol-induced GJICs and Cx43 phosphorylation were inhibited by autophinib or the MEK/ERK pathway inhibitors (Trametinib and FR 180204), indicating that 17ß-estradiol regulated GJICs through the MEK/ERK signaling pathway. In conclusion, 17ß-estradiol improves the autophagy-mediated nuclear maturation with downregulating GJICs and TZPs in porcine COCs. Such an effect occurs by phosphorylation of Cx43, which was regulated via the MEK/ERK signaling pathway.


Assuntos
Conexina 43 , Sistema de Sinalização das MAP Quinases , Animais , Autofagia , Conexina 43/genética , Conexina 43/metabolismo , Estradiol/metabolismo , Estradiol/farmacologia , Feminino , Junções Comunicantes/metabolismo , Meiose , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Oócitos/metabolismo , Fosforilação , Transdução de Sinais , Suínos
9.
Int J Mol Sci ; 22(17)2021 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-34502280

RESUMO

Estrogen receptor alpha (ERα) is a ligand-dependent transcriptional factor in the nuclear receptor superfamily. Many structures of ERα bound with agonists and antagonists have been determined. However, the dynamic binding patterns of agonists and antagonists in the binding site of ERα remains unclear. Therefore, we performed molecular docking, molecular dynamics (MD) simulations, and quantum mechanical calculations to elucidate agonist and antagonist dynamic binding patterns in ERα. 17ß-estradiol (E2) and 4-hydroxytamoxifen (OHT) were docked in the ligand binding pockets of the agonist and antagonist bound ERα. The best complex conformations from molecular docking were subjected to 100 nanosecond MD simulations. Hierarchical clustering was conducted to group the structures in the trajectory from MD simulations. The representative structure from each cluster was selected to calculate the binding interaction energy value for elucidation of the dynamic binding patterns of agonists and antagonists in the binding site of ERα. The binding interaction energy analysis revealed that OHT binds ERα more tightly in the antagonist conformer, while E2 prefers the agonist conformer. The results may help identify ERα antagonists as drug candidates and facilitate risk assessment of chemicals through ER-mediated responses.


Assuntos
Estradiol/metabolismo , Receptor alfa de Estrogênio/agonistas , Receptor alfa de Estrogênio/antagonistas & inibidores , Receptor alfa de Estrogênio/metabolismo , Tamoxifeno/análogos & derivados , Estradiol/química , Receptor alfa de Estrogênio/química , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Ligantes , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Teoria Quântica , Tamoxifeno/química , Tamoxifeno/metabolismo
10.
Cells ; 10(9)2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34571830

RESUMO

Therapeutic use of mesenchymal stem cells (MSCs) for tissue repair has great potential. MSCs from multiple sources, including those derived from human umbilical matrix, namely Wharton's jelly, may serve as a resource for obtaining MSCs. However, low in vivo engraftment efficacy of MSCs remains a challenging limitation. To improve clinical outcomes using MSCs, an in-depth understanding of the mechanisms and factors involved in successful engraftment is required. We recently demonstrated that 17ß-estradiol (E2) improves MSCs in vitro proliferation, directed migration and engraftment in murine heart slices. Here, using a proteomics approach, we investigated the angiogenic potential of MSCs in vivo and the modulatory actions of E2 on mechanisms involved in tissue repair. Specifically, using a Matrigel® plug assay, we evaluated the effects of E2 on MSCs-induced angiogenesis in ovariectomized (OVX) mice. Moreover, using proteomics we investigated the potential pro-repair processes, pathways, and co-mechanisms possibly modified by the treatment of MSCs with E2. Using RT-qPCR, we evaluated mRNA expression of pro-angiogenic molecules, including endoglin, Tie-2, ANG, and VEGF. Hemoglobin levels, a marker for blood vessel formation, were increased in plugs treated with E2 + MSCs, suggesting increased capillary formation. This conclusion was confirmed by the histological analysis of capillary numbers in the Matrigel® plugs treated with E2 + MSC. The LC-MS screening of proteins obtained from the excised Matrigel® plugs revealed 71 proteins that were significantly altered following E2 exposure, 57 up-regulated proteins and 14 down-regulated proteins. A major result was the association of over 100 microRNA molecules (miRNAs) involved in cellular communication, vesicle transport, and metabolic and energy processes, and the high percentage of approximately 25% of genes involved in unknown biological processes. Together, these data provide evidence for increased angiogenesis by MSCs treated with the sex hormone E2. In conclusion, E2 treatment may increase the engraftment and repair potential of MSCs into tissue, and may promote MSC-induced angiogenesis after tissue injury.


Assuntos
Estrogênios/metabolismo , Células-Tronco Mesenquimais/metabolismo , Neovascularização Patológica/metabolismo , Neovascularização Fisiológica/fisiologia , Animais , Diferenciação Celular/fisiologia , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Estradiol/metabolismo , Feminino , Transplante de Células-Tronco Mesenquimais/métodos , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Proteômica/métodos , Geleia de Wharton/metabolismo
11.
Nat Commun ; 12(1): 5565, 2021 09 22.
Artigo em Inglês | MEDLINE | ID: mdl-34552089

RESUMO

Complex autoimmune diseases are sexually dimorphic. An interplay between predisposing genetics and sex-related factors probably controls the sex discrepancy in the immune response, but the underlying mechanisms are unclear. Here we positionally identify a polymorphic estrogen receptor binding site that regulates Cd2 expression, leading to female-specific differences in T cell-dependent mouse models of autoimmunity. Female mice with reduced Cd2 expression have impaired autoreactive T cell responses. T cells lacking Cd2 costimulation upregulate inhibitory Lag-3. These findings help explain sexual dimorphism in human autoimmunity, as we find that CD2 polymorphisms are associated with rheumatoid arthritis and 17-ß-estradiol-regulation of CD2 is conserved in human T cells. Hormonal regulation of CD2 might have implications for CD2-targeted therapy, as anti-Cd2 treatment more potently affects T cells in female mice. These results demonstrate the relevance of sex-genotype interactions, providing strong evidence for CD2 as a sex-sensitive predisposing factor in autoimmunity.


Assuntos
Doenças Autoimunes/genética , Antígenos CD2/genética , Predisposição Genética para Doença/genética , Animais , Artrite Reumatoide/genética , Artrite Reumatoide/imunologia , Doenças Autoimunes/imunologia , Autoimunidade/genética , Autoimunidade/imunologia , Sítios de Ligação/genética , Antígenos CD2/imunologia , Antígenos CD2/metabolismo , Modelos Animais de Doenças , Estradiol/metabolismo , Feminino , Regulação da Expressão Gênica , Humanos , Ativação Linfocitária , Masculino , Camundongos , Polimorfismo Genético , Caracteres Sexuais , Linfócitos T/imunologia
12.
Int J Mol Sci ; 22(18)2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34576257

RESUMO

Although anti-Müllerian hormone (AMH) has classically been correlated with the regression of Müllerian ducts in male mammals, involvement of this growth factor in other reproductive processes only recently come to light. Teleost is the only gnathostomes that lack Müllerian ducts despite having amh orthologous genes. In adult teleost gonads, Amh exerts a role in the early stages of germ cell development in both males and females. Mechanisms involving the interaction of Amh with gonadotropin- and growth factor-induced functions have been proposed, but our overall knowledge regarding Amh function in fish gonads remains modest. In this study, we report on Amh actions in the European sea bass ovary. Amh and type 2 Amh receptor (Amhr2) are present in granulosa and theca cells of both early and late-vitellogenic follicles and cannot be detected in previtellogenic ovaries. Using the Pichia pastoris system a recombinant sea bass Amh has been produced that is endogenously processed to generate a 12-15 kDa bioactive mature protein. Contrary to previous evidence in lower vertebrates, in explants of previtellogenic sea bass ovaries, mature Amh has a synergistic effect on steroidogenesis induced by the follicle-stimulating hormone (Fsh), increasing E2 and cyp19a1a levels.


Assuntos
Hormônio Antimülleriano/química , Hormônio Foliculoestimulante/metabolismo , Ovário/metabolismo , Receptores de Peptídeos/química , Receptores de Fatores de Crescimento Transformadores beta/química , Proteínas Recombinantes/química , Animais , Hormônio Antimülleriano/metabolismo , Bass , Células COS , Chlorocebus aethiops , Estradiol/metabolismo , Feminino , Gonadotropinas/metabolismo , Gônadas/metabolismo , Células da Granulosa/metabolismo , Imunoensaio , Folículo Ovariano/metabolismo , Plasmídeos/metabolismo , Esteroides/metabolismo , Células Tecais/metabolismo , Vitelogênese
13.
Sci Rep ; 11(1): 15794, 2021 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-34349165

RESUMO

Empathy is a multifaceted phenomenon that is difficult to measure. Self-report questionnaires are the most common and well-validated measures while currently no validated protein biomarkers associated with the empathic reaction have been established. Trigger films have been previously used in psychological research to evoke emotions. Thus, in the present randomized cross-over study we investigated the responses of nine salivary biomarkers that have been related to emotions and stress following an empathy triggering and a control film sequence. Additionally, questionnaires for empathy (Saarbrucken Personality Questionnaire (SPQ)) and current mental stress were applied and participants were asked to assess the film protagonists' emotions using the Positive and Negative Affect Schedule. Data from 46 participants were included in the analysis. α-Amylase, IgA, IL-1ß and estradiol showed a significantly different response between the empathy and control intervention. Moreover, normalized levels of these biomarkers significantly correlated with single scales of the SPQ (control film sequence: α-amylase and IgA with personal distress; estradiol with empathic concern; IL-1ß with fantasy; empathy triggering film sequence: IgA with empathic concern, fantasy and the total empathy score). These findings indicated that the observed changes in salivary biomarker levels were reflective of a physiological response to the empathy triggering film sequence. Future studies using different triggers and settings will show if the identified biomarkers can be considered as surrogate markers for empathic reactions in general.


Assuntos
Emoções/fisiologia , Empatia/fisiologia , Estradiol/metabolismo , Interleucina-1beta/metabolismo , Saliva/metabolismo , alfa-Amilases/metabolismo , Adulto , Biomarcadores/metabolismo , Estudos Cross-Over , Fantasia , Feminino , Humanos , Masculino , Projetos Piloto , Inquéritos e Questionários , Adulto Jovem
14.
Commun Biol ; 4(1): 954, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376799

RESUMO

Longitudinal menstrual cycle studies allow to investigate the effects of ovarian hormones on brain organization. Here, we use spectral dynamic causal modelling (spDCM) in a triple network model to assess effective connectivity changes along the menstrual cycle within and between the default mode, salience and executive control networks (DMN, SN, and ECN). Sixty healthy young women were scanned three times along their menstrual cycle, during early follicular, pre-ovulatory and mid-luteal phase. Related to estradiol, right before ovulation the left insula recruits the ECN, while the right middle frontal gyrus decreases its connectivity to the precuneus and the DMN decouples into anterior/posterior parts. Related to progesterone during the mid-luteal phase, the insulae (SN) engage to each other, while decreasing their connectivity to parietal ECN, which in turn engages the posterior DMN. When including the most confident connections in a leave-one out cross-validation, we find an above-chance prediction of the left-out subjects' cycle phase. These findings corroborate the plasticity of the female brain in response to acute hormone fluctuations and may help to further understand the neuroendocrine interactions underlying cognitive changes along the menstrual cycle.


Assuntos
Estradiol/metabolismo , Ciclo Menstrual/fisiologia , Vias Neurais/fisiologia , Progesterona/metabolismo , Adulto , Mapeamento Encefálico , Feminino , Humanos , Adulto Jovem
15.
Sci Rep ; 11(1): 16287, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381107

RESUMO

Hyperandrogenic women with PCOS show disrupted decidualization (DE) and placentation. Dihydrotestosterone (DHT) is reported to enhance DE in non-PCOS endometrial stromal cells (eSCCtrl); however, this has not been assessed in PCOS cells (eSCPCOS). Therefore, we studied the transcriptome profile of non-decidualized (non-DE) and DE eSCs from women with PCOS and Ctrl in response to short-term estradiol (E2) and/or progesterone (P4) exposure with/without (±) DHT. The non-DE eSCs were subjected to E2 ± DHT treatment, whereas the DE (0.5 mM 8-Br-cAMP, 96 h) eSCs were post-treated with E2 and P4 ± DHT, and RNA-sequenced. Validation was performed by immunofluorescence and immunohistochemistry. The results showed that, regardless of treatment, the PCOS and Ctrl samples clustered separately. The comparison of DE vs. non-DE eSCPCOS without DHT revealed PCOS-specific differentially expressed genes (DEGs) involved in mitochondrial function and progesterone signaling. When further adding DHT, we detected altered responses for lysophosphatidic acid (LPA), inflammation, and androgen signaling. Overall, the results highlight an underlying defect in decidualized eSCPCOS, present with or without DHT exposure, and possibly linked to the altered pregnancy outcomes. We also report novel factors which elucidate the mechanisms of endometrial dysfunction in PCOS.


Assuntos
Androgênios/metabolismo , Endométrio/metabolismo , Síndrome do Ovário Policístico/metabolismo , Células Estromais/metabolismo , Adulto , Di-Hidrotestosterona/metabolismo , Estradiol/metabolismo , Feminino , Humanos , Gravidez , Progesterona/metabolismo , Transdução de Sinais/fisiologia
16.
Anim Sci J ; 92(1): e13617, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34405917

RESUMO

Granulosa cells (GCs) play an important role in the development of follicles. In this study, we investigate the impact of heat stress at 41°C and 43°C on duck GCs' proliferation and steroids secretion. And, the transcriptomic responses to heat treatment were examined using RNA-sequencing analysis. Digital gene expression profiling was used to screen and identify differentially expressed genes (fold change ≥ 2 and Q value < 0.05). Further, the differential expression genes (DEGs) were classified into GO categories and KEGG pathways. The results show that duck GCs blocked in the G1 phase were increased on exposure to heat stress. Meanwhile, the expression of proliferative genes, which were essential for the transition from G1 to S phase, was inhibited. At the same time, heat stress inhibited the estradiol synthesis of GCs by decreasing CYP11A1 and CYP19A1 gene expression. A total of 241 DEGs including 181 upregulated and 60 downregulated ones were identified. Transcriptome result shows that heat shock protein and CXC chemokines gene were significantly activated during heat stress. While collagenases (MMP1 and MMP13) and strome lysins (MMP3) were downregulated. And, the hedgehog signaling pathway may be a prosurvival adaptive response under heat stress. These results offer a basis for better understanding the molecular mechanism underlying lay-eggs-less in ducks under heat stress.


Assuntos
Proliferação de Células/genética , Patos/fisiologia , Estradiol/metabolismo , Regulação da Expressão Gênica no Desenvolvimento/genética , Expressão Gênica , Células da Granulosa/fisiologia , Resposta ao Choque Térmico/genética , Resposta ao Choque Térmico/fisiologia , Ovulação/fisiologia , Animais , Aromatase/genética , Aromatase/metabolismo , Quimiocinas CXC/genética , Quimiocinas CXC/metabolismo , Enzima de Clivagem da Cadeia Lateral do Colesterol/genética , Enzima de Clivagem da Cadeia Lateral do Colesterol/metabolismo , Regulação para Baixo , Feminino , Células da Granulosa/metabolismo , Proteínas de Choque Térmico/metabolismo , Proteínas Hedgehog/metabolismo , Metaloproteinase 1 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/fisiologia
17.
Cells ; 10(8)2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34440676

RESUMO

Estradiol exerts neuroprotective actions that are mediated by the regulation of a variety of signaling pathways and homeostatic molecules. Among these is neuroglobin, which is upregulated by estradiol and translocated to the mitochondria to sustain neuronal and glial cell adaptation to injury. In this paper, we will discuss the role of neuroglobin in the neuroprotective mechanisms elicited by estradiol acting on neurons, astrocytes and microglia. We will also consider the role of neuroglobin in the neuroprotective actions of clinically relevant synthetic steroids, such as tibolone. Finally, the possible contribution of the estrogenic regulation of neuroglobin to the generation of sex differences in brain pathology and the potential application of neuroglobin as therapy against neurological diseases will be examined.


Assuntos
Encefalopatias/tratamento farmacológico , Encéfalo/efeitos dos fármacos , Estradiol/uso terapêutico , Estrogênios/uso terapêutico , Neuroglobina/metabolismo , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/uso terapêutico , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Encefalopatias/metabolismo , Encefalopatias/patologia , Estradiol/metabolismo , Feminino , Humanos , Masculino , Neurônios/metabolismo , Neurônios/patologia , Fatores Sexuais , Transdução de Sinais
18.
Biomed Pharmacother ; 139: 111658, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34243627

RESUMO

According to recent statistics, Lung Cancer (LC) is one of the most frequently diagnosed tumor types, representing nearly 12% of all global cancer cases. Moreover, in recent years, an increased mortality rate and incidence of this cancer were observed, especially among nonsmokers. Lung cancer patients are often characterized by poor prognosis and low survival rates, which encourages the scientific community to investigate the biochemical and molecular processes leading to the development of this malignancy. Furthermore, the mechanisms of LC formation and progression are not yet fully elucidated due to their high complexity, as well as a multitude of environmental, genetic, and molecular factors involved. Even though LC's association with exposure to cigarette smoke is indisputable, current research provides evidence that the development of this cancer can also be affected by the presence of estrogens and their interaction with several tobacco smoke components. Hence, the main goal of this brief review was to investigate reports of a possible synergy between 17ß estradiol (E2), the most biologically active estrogen, and benzo(a)pyrene (BaP), a strongly carcinogenic compound produced as a result of incomplete tobacco combustion. The literature sources demonstrate a possible carcinogenic synergy between estrogens, especially E2, and BaP, a toxic tobacco smoke component. Therefeore, the combined effect of disturbed estrogen production in cancer cells, as well as the molecular influence exerted by BaP, could explain the increased aggressiveness and rate of LC development. Summarizing, the synergistic effect of these risk factors is an interesting area of further research.


Assuntos
Benzo(a)pireno/toxicidade , Estrogênios/metabolismo , Neoplasias Pulmonares/induzido quimicamente , Neoplasias Pulmonares/metabolismo , Fumar/efeitos adversos , Animais , Carcinógenos/toxicidade , Estradiol/metabolismo , Humanos , Fumaça/efeitos adversos , Tabaco/toxicidade
19.
Taiwan J Obstet Gynecol ; 60(4): 658-664, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34247803

RESUMO

OBJECTIVE: Endometriosis is an estrogen-dependent, benign, and chronic gynecological disorder occurring in women of reproductive age. Although the pathogenesis of endometriosis is poorly understood, implantation theory indicates that viable endometrial cells shed from the endometrium into the pelvic peritoneum or ovaries, possibly through retrograde menstruation, and then reattach, invade, and damage other tissues. Interleukin (IL)-33, a new member of the IL-1 superfamily, is mainly upregulated by stromal cells following proinflammatory stimulation. Matrix metalloproteinases (MMPs) are involved in the degradation and reconstruction of the extracellular matrix. MMP-9 participates in the pathogenesis of endometriosis by promoting the invasion of endometriotic cells. This study investigated the effect of IL-33 on the cell invasion ability of and MMP-9 expression in human stromal cells derived from ovarian endometrioma (hOVEN-SCs). MATERIALS AND METHODS: We isolated hOVEN-SCs from human ovarian endometrioma. Gene expression was analyzed using the Illumina Human WG-6 v2 Expression BeadChips microarray platform and through reverse transcription-polymerase chain reaction. Cell migration and invasion were examined by performing the transwell chamber assay. RESULTS: We found that 17ß-estradiol could increase the expression of IL-33 and ST2 through the estrogen receptor pathway in hOVEN-SCs. Moreover, IL-33 upregulated MMP-9 expression in and enhanced the invasion ability of hOVEN-SCs through the ST2/MAPK signaling pathway. Our results showed that MMP-9 expression was essential for IL-33-induced cell invasion. CONCLUSION: Our main finding is that 17ß-estradiol could increase IL-33 expression through the estrogen receptor pathway and activate MMP-9 expression in and invasion ability of hOVEN-SCs through the IL-33/ST2/MAPK signaling pathway. The results of this study and further related studies may provide new strategies for the prevention and treatment of endometriosis.


Assuntos
Endometriose/genética , Endométrio/citologia , Interleucina-33/metabolismo , Sistema de Sinalização das MAP Quinases/genética , Células Estromais/fisiologia , Movimento Celular/genética , Células Cultivadas , Estradiol/metabolismo , Feminino , Humanos , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Ovário/citologia
20.
Int J Mol Sci ; 22(13)2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34203300

RESUMO

Pain symptoms in temporomandibular disorders (TMD) predominantly affect reproductive women, suggesting that estrogen regulates pain perception. However, how estrogen contributes to chronic TMD pain remains largely unclear. In the present study, we performed behavioral tests, electrophysiology, Western blot and immunofluorescence to investigate the role and underlying mechanisms of estrogen in dental experimental occlusal interference (EOI)-induced chronic masseter mechanical hyperalgesia in rats. We found that long-term 17ß-estradiol (E2) replacement exacerbated EOI-induced masseter hyperalgesia in a dose-dependent manner in ovariectomized (OVX) rats. Whole-cell patch-clamp recordings demonstrated that E2 (100 nM) treatment enhanced the excitability of isolated trigeminal ganglion (TG) neurons in OVX and OVX EOI rats, and EOI increased the functional expression of transient receptor potential vanilloid-1 (TRPV1). In addition, E2 replacement upregulated the protein expression of TRPV1 in EOI-treated OVX rats. Importantly, intraganglionic administration of the TRPV1 antagonist AMG-9810 strongly attenuated the facilitatory effect of E2 on EOI-induced masseter mechanical sensitivity. These results demonstrate that E2 exacerbated EOI-induced chronic masseter mechanical hyperalgesia by increasing TG neuronal excitability and TRPV1 function. Our study helps to elucidate the E2 actions in chronic myogenic TMD pain and may provide new therapeutic targets for relieving estrogen-sensitive pain.


Assuntos
Hiperalgesia/tratamento farmacológico , Neurônios Aferentes/efeitos dos fármacos , Canais de Cátion TRPV/metabolismo , Gânglio Trigeminal/metabolismo , Acrilamidas/farmacologia , Animais , Western Blotting , Compostos Bicíclicos Heterocíclicos com Pontes/farmacologia , Estradiol/genética , Estradiol/metabolismo , Feminino , Imunofluorescência , Hiperalgesia/metabolismo , Ovariectomia , Ratos , Ratos Sprague-Dawley , Gânglio Trigeminal/efeitos dos fármacos
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