Search results for: Aromatase
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Molecular basis of CYP19A1 deficiency in a 46, XX patient with R550W mutation in POR: Expanding the PORD phenotype.Mutations in Cytochrome P450 oxidoreductase (POR) cause a form of congenital adrenal hyperplasia (CAH). We are reporting a novel R550W mutation in POR identified in a 46, XX patient with signs of aromatase deficiency.
1591 related Products with: Molecular basis of CYP19A1 deficiency in a 46, XX patient with R550W mutation in POR: Expanding the PORD phenotype.Goat Anti-Human Aromatase Multiple organ tumor tiss FDA Standard Frozen Tissu Thermal Shaker with cooli FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu FDA Standard Frozen Tissu STAT1 & FRAP1 Protein Pro Rectum adenocarcinoma tis Rabbit Anti-Cell death in
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Identification of PARP-1, Histone H1 and SIRT-1 as New Regulators of Breast Cancer-Related Aromatase Promoter I.3/II.Paracrine interactions between malignant estrogen receptor positive (ER) breast cancer cells and breast adipose fibroblasts (BAFs) stimulate estrogen biosynthesis by aromatase in BAFs. In breast cancer, mainly the cAMP-responsive promoter I.3/II-region mediates excessive aromatase expression. A rare single nucleotide variant (SNV) in this promoter region, which caused 70% reduction in promoter activity, was utilized for the identification of novel regulators of aromatase expression. To this end, normal and mutant promoter activities were measured in luciferase reporter gene assays. DNA-binding proteins were captured by DNA-affinity and identified by mass spectrometry. The DNA binding of proteins was analyzed using electrophoretic mobility shift assays, immunoprecipitation-based in vitro binding assays and by chromatin immunoprecipitation in BAFs in vivo. Protein expression and parylation were analyzed by western blotting. Aromatase activities and RNA-expression were measured in BAFs. Functional consequences of poly (ADP-ribose) polymerase-1 (PARP-1) knock-out, rescue or overexpression, respectively, were analyzed in murine embryonic fibroblasts (MEFs) and the 3T3-L1 cell model. In summary, PARP-1 and histone H1 (H1) were identified as critical regulators of aromatase expression. PARP-1-binding to the SNV-region was crucial for aromatase promoter activation. PARP-1 parylated H1 and competed with H1 for DNA-binding, thereby inhibiting its gene silencing action. In MEFs (PARP-1 knock-out and wild-type) and BAFs, PARP-1-mediated induction of the aromatase promoter showed bi-phasic dose responses in overexpression and inhibitor experiments, respectively. The HDAC-inhibitors butyrate, panobinostat and selisistat enhanced promoter I.3/II-mediated gene expression dependent on PARP-1-activity. Forskolin stimulation of BAFs increased promoter I.3/II-occupancy by PARP-1, whereas SIRT-1 competed with PARP-1 for DNA binding but independently activated the promoter I.3/II. Consistently, the inhibition of both PARP-1 and SIRT-1 increased the NAD/NADH-ratio in BAFs. This suggests that cellular NAD/NADH ratios control the complex interactions of PARP-1, H1 and SIRT-1 and regulate the interplay of parylation and acetylation/de-acetylation events with low NAD/NADH ratios (reverse Warburg effect), promoting PARP-1 activation and estrogen synthesis in BAFs. Therefore, PARP-1 inhibitors could be useful in the treatment of estrogen-dependent breast cancers.
1514 related Products with: Identification of PARP-1, Histone H1 and SIRT-1 as New Regulators of Breast Cancer-Related Aromatase Promoter I.3/II.Anti-Breast Cancer Resist Monoclonal Anti Breast Ca Monoclonal Anti Breast Ca Universal Colorimetric PA Monoclonal Anti-Breast Ca Anti Breast Cancer Resist Monoclonal Anti-Breast Ca Breast cancer membrane pr Universal Chemiluminescen anti Aspartate Transamina MS-275 (Entinostat) Mecha Androgen Receptor
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Management of Male Breast Cancer: ASCO Guideline.To develop recommendations concerning the management of male breast cancer.
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Auditory learning in an operant task with social reinforcement is dependent on neuroestrogen synthesis in the male songbird auditory cortex.Animals continually assess their environment for cues associated with threats, competitors, allies, mates or prey, and experience is crucial for those associations. The auditory cortex is important for these computations to enable valence assignment and associative learning. The caudomedial nidopallium (NCM) is part of the songbird auditory association cortex and it is implicated in juvenile song learning, song memorization, and song perception. Like human auditory cortex, NCM is a site of action of estradiol (E2) and is enriched with the enzyme aromatase (E2-synthase). However, it is unclear how E2 modulates auditory learning and perception in the vertebrate auditory cortex. In this study we employ a novel, auditory-dependent operant task governed by social reinforcement to test the hypothesis that neuro-E2 synthesis supports auditory learning in adult male zebra finches. We show that local suppression of aromatase activity in NCM disrupts auditory association learning. By contrast, post-learning performance is unaffected by either NCM aromatase blockade or NCM pharmacological inactivation, suggesting that NCM E2 production and even NCM itself are not required for post-learning auditory discrimination or memory retrieval. Therefore, neuroestrogen synthesis in auditory cortex supports the association between sounds and behaviorally relevant consequences.
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Administration of pharmaceutical agents prior to testicular sperm extraction procedures: A meaningful or meaningless approach?To date, no randomized and controlled study has demonstrated effect of adjuvant medical therapy on testicular sperm production before the sperm retrieval procedures in men with non-obstructive azoospermia (NOA).
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Efficacy and safety of ultra-low dose 0.005% estriol vaginal gel for the treatment of vulvovaginal atrophy in postmenopausal women with early breast cancer treated with nonsteroidal aromatase inhibitors: a phase II, randomized, double-blind, placebo-controlled trial.To assess the efficacy and safety of ultra-low dose 0.005% estriol vaginal gel in women with breast cancer receiving nonsteroidal aromatase inhibitors (NSAIs) and experiencing treatment-related vulvovaginal symptoms and signs.
2032 related Products with: Efficacy and safety of ultra-low dose 0.005% estriol vaginal gel for the treatment of vulvovaginal atrophy in postmenopausal women with early breast cancer treated with nonsteroidal aromatase inhibitors: a phase II, randomized, double-blind, placebo-controlled trial.Syringe pump can be contr Breast cancer tissue arra Breast cancer tissue arra Middle advanced stage bre Breast cancer tissue arra Breast cancer and normal Breast cancer tissue arra Breast cancer tissue arra Breast cancer and matched Breast cancer, carcinoma Late stage breast cancer Breast cancer (IDC) tissu
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Acidic Exopolysaccharide Produced from Marine 3MS 2017 for the Protection and Treatment of Breast Cancer.This study was planned to investigate the anti-breast-cancer property of acidic exopolysaccharide produced from marine 3MS 2017 (BAEPS) in an animal model, which previously showed in-vitro anti-breast-cancer activity, by studying its potential participation in various targeted mechanisms.
1179 related Products with: Acidic Exopolysaccharide Produced from Marine 3MS 2017 for the Protection and Treatment of Breast Cancer.Anti-Breast Cancer Resist Monoclonal Anti Breast Ca Monoclonal Anti Breast Ca Monoclonal Anti-Breast Ca Anti Breast Cancer Resist Monoclonal Anti-Breast Ca Breast cancer test tissue Breast cancer and normal Breast cancer tissue arra Breast invasive ductal ca Tissue microarray of brea Breast cancer test tissue
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Aromatase Inhibition Ameliorates Decreased LH Output Found in Obese Women.In obese ovulatory women, serum luteinizing Hormone (LH) and follicle stimulating hormone (FSH) are lowered compared with normal weight women. This relative hypogonadotropic hypogonadism represents a potential etiology for overall decreased fertility in obesity. The objective was to determine if administration of an aromatase inhibitor (AI) to ovulating obese women would normalize LH and FSH by interrupting estradiol negative feedback. Letrozole (2.5-5 mg) was given daily to 22 women, 12 obese and 10 normal weight, for 7 days. On the last day of administration, 8 h of blood sampling was done every 10 min before and after a bolus of GnRH at 4 h. We obtained data from 21 ovulatory women (10 normal weight and 11 obese) who had undergone a similar protocol of frequent blood sampling but no aromatase inhibitors (AI) treatment. Serum LH and FSH levels and pulse characteristics were measured. Treatment with AI only significantly affected obese women. Further, in women with obesity, LH secretion, prior to the GnRH bolus, was significantly higher in AI treated compared with non-treated (p = 0.011). AI treatment doubled LH pulse amplitude in obese women (p = 0.004). In response to aromatase inhibition, LH secretion in ovulatory women with obesity is increased and similar to levels found in untreated normal weight women. The increase in LH pulse amplitude indicates that the AI effect is mediated at the level of the pituitary. Our results suggest that the hypogonadotropic phenotype of simple obesity is subject to modulation by interruption of estradiol negative feedback.
1404 related Products with: Aromatase Inhibition Ameliorates Decreased LH Output Found in Obese Women.Directed In Vivo Angiogen EpiQuik Superoxide Dism EpiQuik Histone Methyltra EpiQuik MBD2 Binding Ac Mouse Anti-Lipoprotein Li EpiQuik Histone Methyltra Goat Anti-Human Aromatase EpiQuik Histone Methyltra EpiQuik MBD2 Binding Acti EpiQuik Superoxide Dism EpiQuik Histone Methyltra EpiQuik Histone Methyltra
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Lipotoxicity Impairs Granulosa Cell Function Through Activated Endoplasmic Reticulum Stress Pathway.Obesity is closely related to reproductive disorders, which may eventually lead to infertility in both males and females. Ovarian granulosa cells play a critical role during the maintenance of oocyte development through the generation of sex steroids (mainly estradiol and progesterone) and different kinds of growth factors. However, the molecular mechanism of obesity-induced granulosa cell dysfunction remains poorly investigated. In our current study, we observed that high-fat diet feeding significantly increased the level of glucose-regulated protein 78 kDa (GRP78) protein expression in mouse granulosa cells; testosterone-induced estradiol generation was impaired accordingly. To further evaluate the precise mechanism of lipotoxicity-induced granulosa cell dysfunction, mouse primary granulosa cells were treated with palmitate, and the expression levels of ER stress markers were evaluated by real-time PCR and western blot. Lipotoxicity significantly increased ER stress but impaired the mRNA expression of granulosa cell function-related makers, including androgen receptor (Ar), cytochrome P450 family 19 subfamily A member 1 (Cyp19a1), hydroxysteroid 17-beta dehydrogenase 1 (Hsd17b1), and insulin receptor substrate 1 (Irs1). Impaired testosterone-induced estradiol generation was also observed in cultured mouse granulosa cells after palmitate treatment. Insulin augmented testosterone induced estradiol generation through activation of the AKT pathway. However, palmitate treatment abolished insulin-promoted aromatase expression and estradiol generation by the stimulation of ER stress. Overexpression of IRS1 significantly ameliorated palmitate- or tunicamycin-induced impairment of aromatase expression and estradiol generation. Taken together, our current study demonstrated that lipotoxicity impaired insulin-stimulated estradiol generation through activated ER stress and inhibited IRS1 pathway.
2681 related Products with: Lipotoxicity Impairs Granulosa Cell Function Through Activated Endoplasmic Reticulum Stress Pathway.stress-associated endopla Tissue array of ovarian g anti Transferrin receptor Nrf antioxidant pathway A Mouse Anti-Rat Reticulum Human Phospho-EGFR (Activ Wnt Signaling Pathway TCF AP-1 Reporter – HEK293 anti CD38 Hematopoietic p JAK pathway ISRE reporter Mouse Anti-Rat Reticulum T-Cell Receptor Signaling
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Towards an Understanding of the Mode of Action of Human Aromatase Activity for Azoles through Quantum Chemical Descriptors-Based Regression and Structure Activity Relationship Modeling Analysis.Aromatase is an enzyme member of the cytochrome P450 superfamily coded by the CYP19A1 gene. Its main action is the conversion of androgens into estrogens, transforming androstenedione into estrone and testosterone into estradiol. This enzyme is present in several tissues and it has a key role in the maintenance of the balance of androgens and estrogens, and therefore in the regulation of the endocrine system. With regard to chemical safety and human health, azoles, which are used as agrochemicals and pharmaceuticals, are potential endocrine disruptors due to their agonist or antagonist interactions with the human aromatase enzyme. This theoretical study investigated the active agonist and antagonist properties of "chemical classes of azoles" to determine the relationships of azole interaction with CYP19A1, using stereochemical and electronic properties of the molecules through classification and multilinear regression (MLR) modeling. The antagonist activities for the same substituent on diazoles and triazoles vary with its chemical composition and its position and both heterocyclic systems require aromatic substituents. The triazoles require the spherical shape and diazoles have to be in proper proportion of the branching index and the number of ring systems for the inhibition. Considering the electronic aspects, triazole antagonist activity depends on the electrophilicity index that originates from interelectronic exchange interaction () and the LUMO energy ( E LUMO PM 7 ), and the diazole antagonist activity originates from the penultimate orbital ( E HOMONL PM 7 ) of diazoles. The regression models for agonist activity show that it is opposed by the static charges but favored by the delocalized charges on the diazoles and thiazoles. This study proposes that the electron penetration of azoles toward heme group decides the binding behavior and stereochemistry requirement for antagonist activity against CYP19A1 enzyme.
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