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Search results for: Androgen Receptor

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#34555425   2021/09/20 To Up

Androgens promote vascular endothelial cell proliferation through activation of a ZIP9-dependent inhibitory G protein/PI3K-Akt/Erk/cyclin D1 pathway.

While androgens have been reported to mediate cardiovascular endothelial cell proliferation, the potential involvement of membrane androgen receptors (mAR) has not been examined. Here we show ZIP9, a recently characterized mAR, mediates androgen-induced early proliferative events in human umbilical vein endothelial cells (HUVECs). Androgen treatment significantly increased cyclin D1 nuclear localization and proliferation, which were blocked by transfection with siRNA targeting ZIP9 but not the nuclear AR. Testosterone rapidly activated inhibitory G protein signaling, Erk, and Akt, and inhibition of these signaling members abrogated the ZIP9-mediated cyclin D1 and proliferative responses. Erk and Akt modulated cyclin D1 nuclear localization by upregulation of cyclin D1 mRNA and inhibition of GSK-3β activity, respectively. This is the first study to demonstrate a role for ZIP9 in HUVEC proliferation and indicates ZIP9 is a physiologically-relevant androgen receptor in the cardiovascular system that merits further study as a potential therapeutic target for treating cardiovascular disease.
Aubrey Converse, Peter Thomas

2775 related Products with: Androgens promote vascular endothelial cell proliferation through activation of a ZIP9-dependent inhibitory G protein/PI3K-Akt/Erk/cyclin D1 pathway.

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#34555414   2021/09/20 To Up

Sexually dimorphic expression of sexual differentiation genes in the internal genital organs of Japanese quail embryos.

Japanese quail (Coturnix japonica) is an avian model used to evaluate the reproductive and developmental toxicity of chemicals. The National Institute for Environmental Studies (NIES) of Japan established a strain of Japanese quail, NIES-L, which may be a better model because of its highly inbred characteristics. To understand sexual differentiation of the reproductive organs and the value of using NIES-L quails for avian toxicity assessment, we profiled estradiol and androgen plasma levels by enzyme-linked immunosorbent assay; the mRNA levels of estrogen receptor-α (ERα), ERβ, and androgen receptor (AR) in the gonads, Müllerian ducts, Wolffian ducts; and the mRNA levels of steroidogenic enzymes, cholesterol side chain cleavage enzyme (P450), 17α-hydroxylase/C lyase (P450), 3β-hydroxysteroid dehydrogenase (3β-HSD), 17β-hydroxysteroid dehydrogenase (17β-HSD), and aromatase (P450), anti-Müllerian hormone (AMH), and AMH receptor type 2 (AMHR2) in the gonads of NIES-L Japanese quails on embryonic days 9, 12, and 15 using a real-time quantitative PCR method. The plasma estradiol concentration was higher in females than males on these embryonic days, but no sex difference was found in the plasma androgens. The mRNA levels of all examined steroidogenic enzymes were significantly higher in female than male embryos. In particular, the P450 mRNA levels showed a striking sex difference: P450 was expressed in female but not male gonads. In contrast, the AMH and AMHR2 mRNA levels in the gonads were higher in males than females. The ERα, ERβ, and AR mRNA levels increased in the left female gonad and peaked on embryonic day 15, but not in the left and right male gonads; therefore, there was a female-biased sex difference. The ERα, ERβ, and AR mRNA levels in the left Müllerian duct, but not in the right Müllerian duct, of females increased and peaked on embryonic day 15, which resulted in asymmetric mRNA levels. The Wolffian ducts expressed ERα, ERβ, and AR in both sexes, and no sex difference or asymmetry of mRNA levels was found. The information obtained from this study helps elucidate the molecular endocrinological basis of sexual dimorphism formation of reproductive organs and clarify the value of NIES-L quails for toxicity assessment.
Shinji Tsukahara, Masahiro Morishita, Shiho Sasaki, Kanta Wakayama, Kaito Kobayashi, Koichi Ohno, Takaharu Kawashima

1554 related Products with: Sexually dimorphic expression of sexual differentiation genes in the internal genital organs of Japanese quail embryos.

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#34555281   2021/09/23 To Up

Enhanced Properties of a Benzimidazole Benzylpyrazole Lysine Demethylase Inhibitor: Mechanism-of-Action, Binding Site Analysis, and Activity in Cellular Models of Prostate Cancer.

Jumonji domain-containing lysine demethylase (KDM) enzymes are encoded by genes of the KDM superfamily. Activities of the KDM4 subfamily promote aggressive phenotypes associated with prostate cancer (PCa). Previously, we discovered a benzimidazole pyrazole molecule that inhibited KDM4 isoforms with properties tractable for development. Here, we demonstrate that a benzyl-substituted variant of this inhibitor exhibits improved potency in biochemical assays, is cell-permeable, and kills PCa cells at low micromolar concentrations. By X-ray crystallography and kinetics-based assays, we demonstrate that the mechanism of inhibition is complex, proceeding via competition with the enzyme for binding of active-site Fe and by populating a distal site on the enzyme surface. Furthermore, we provide evidence that the inhibitor's cytostatic properties arise from direct intracellular inhibition of KDM4 enzymes. PCa cells treated with the inhibitor exhibit reduced expression of genes regulated by the androgen receptor, an outcome accompanied by epigenetic maintenance of a heterochromatic state.
David M Carter, Edgar Specker, Piotr H Małecki, Jessica Przygodda, Krystyna Dudaniec, Manfred S Weiss, Udo Heinemann, Marc Nazaré, Ulrich Gohlke

1017 related Products with: Enhanced Properties of a Benzimidazole Benzylpyrazole Lysine Demethylase Inhibitor: Mechanism-of-Action, Binding Site Analysis, and Activity in Cellular Models of Prostate Cancer.

100 ul96T

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#34552789   2021/08/09 To Up

Testosterone treatment improves liver function and reduces cardiovascular risk: A long-term prospective study.

: To report the association between testosterone treatment in hypogonadal men with hepatic steatosis, non-alcoholic fatty liver disease and cardiovascular disease (CVD). A prospective study was conducted to assess the physiological and functional performance of the long-term effects of testosterone undecanoate treatment on hepatic steatosis in 496 hypogonadal men. Two groups were studied, the treatment group (T-group) of 312 patients treated with TU 1000 mg every 12 weeks and followed for 8 years, and an untreated control group (C-group) of 184 patients. We evaluated liver functions and Fatty Liver Index (FLI) according to Mayo Clinic parameters and guidelines. The T-group showed a decrease in the FLI (from a mean [SD] of 83.70 [12.15] to 67.12 [19.21]), bilirubin (from a mean [SD] of 1.69 [4.21] to 1.31 [1.91] mg/dL), triglycerides (from a mean [SD] of 254.87 [92.99] to 213.37 [66.91] mg/dL), and gamma-glutamyl-transferase (from a mean [SD] of 39.45 [11.51] to 29.11 [7.68] U/L) over the duration of the study. Other parameters were also reduced in the T-group such as body mass index (from a mean [SD] of 31.59 [4.51] to 29.50 [3.84] kg/m) and waist circumference (from a mean [SD] of 107.51 [9.95] to 101.86 [9.28] cm). A total of 25 deaths (7.8%) were recorded in the T-group, among them, 11 (44%) were related to CVD. While in the C-group 28 deaths (15.2%) were recorded and all the reported deaths (100%) were related to CVD. The findings suggest that long-term testosterone therapy in hypogonadal men improves liver function. While, the physiological and functional improvements in the liver may be associated with a decrease in CVD-related mortality. Abbreviations ALT: alanine transaminase; AR: androgen receptor; AST: aspartate transaminase; BMI: body mass index; CVD: cardiovascular disease; FLI: Fatty Liver Index; γ-GT: gamma-glutamyl-transferase; MetS: metabolic syndrome; LDL: low-density lipoprotein; NAFLD: non-alcoholic fatty liver disease; RCT: randomised controlled trial; T2DM: type II diabetes mellitus; TT: total testosterone; TTh: testosterone therapy; TU: testosterone undecanoate; WC: waist circumference.
Ahmad Al-Qudimat, Raed M Al-Zoubi, Aksam A Yassin, Mustafa Alwani, Omar M Aboumarzouk, Khaled AlRumaihi, Raidh Talib, Abdulla Al Ansari

2518 related Products with: Testosterone treatment improves liver function and reduces cardiovascular risk: A long-term prospective study.

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#34552772   2021/07/24 To Up

Medical management of non-obstructive azoospermia: A systematic review.

While most men with non-obstructive azoospermia (NOA) are not amenable to medical treatment, some men can be treated effectively with hormonal therapy, prior to considering surgery. In some cases, hormonal therapy alone can treat NOA, without the need for surgery. In other cases, correction of a potential hormonal imbalance can enhance the chances of success of surgical sperm retrieval (SSR), with either conventional or microdissection testicular sperm extraction. Abnormal testicular function and low androgen levels can result from a primary dysfunction, a medical or surgical condition, or from an exogenous factor, and should be managed prior to more invasive interventions. Even men with normal androgen levels may benefit from hormonal therapy before sperm retrieval. Moreover, SSR may cause testicular injury and aggravate the pre-existing situation. If surgical extraction of sperm fails, it leaves the patients with less satisfactory options, like donor sperm or adoption. Therefore, it is the role of the infertility specialist to be vigilant and identify reversible causes of NOA, such as hormonal imbalance, prior to considering surgery. In the present paper we will systematically review the literature and highlight the available conventional medical regimens, as well as experimental ones. : ART: assisted reproductive technology; CAH: congenital adrenal hyperplasia; EAU: European Association of Urology; hCG: human chorionic gonadotrophin; HH: hypogonadotrophic hypogonadism; hMG: human menopausal gonadotrophin; IUI: intrauterine insemination; micro-TESE: microdissection testicular sperm extraction; NOA: non-obstructive azoospermia; OR: odds ratio; SCO: Sertoli-cell only; SERM: selective oestrogen receptor modulator; SRR: sperm retrieval rate; SSC: spermatogonia stem cell; TART: testicular adrenal rest tumour; WMD: weighted mean difference.
Mohammad H Alkandari, Armand Zini

1502 related Products with: Medical management of non-obstructive azoospermia: A systematic review.

2 mg100ug Lyophilized100ug Lyophilized200 100.00 ug 5 G1 mg100μl1ml100ug100ug Lyophilized1000

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#34552120   2021/09/22 To Up

Wuzi-Yanzong prescription alleviates spermatogenesis disorder induced by heat stress dependent on Akt, NF-κB signaling pathway.

Akt and nuclear factor kappa B (NF-κB) signaling pathways are involved in germ cell apoptosis and inflammation after testicular heat stress (THS). We observed that after THS induced by the exposure of rat testes to 43 °C for 20 min, their weight decreased, the fraction of apoptotic testicular germ cells significantly increased, and the proliferation of germ cells was inhibited. In addition, THS lowered serum testosterone (T) level, whereas the levels of follicle stimulating hormone and luteinizing hormone were not significantly changed. The ultrastructure of the seminiferous tubules became abnormal after THS, the structure of the blood-testis barrier (BTB) became loose, and the Sertoli cells showed a trend of differentiation. The level of phosphorylated Akt was reduced, whereas the amount of phosphorylated NF-κB p65 was augmented by THS. Wuzi-Yanzong (WZYZ), a classic Chinese medicine prescription for the treatment of male reproductive dysfunctions, alleviated the changes induced by THS. In order to determine the mechanism of action of WZYZ, we investigated how this preparation modulated the levels of T, androgen receptor (AR), erythropoietin (EPO), EPO receptor, and Tyro-3, Axl, and Mer (TAM) family of tyrosine kinase receptors. We found that WZYZ activated the Akt pathway, inhibited the Toll-like receptor/MyD88/NF-κB pathway, and repaired the structure of BTB by regulating the levels of T, AR, TAM receptors, and EPO. In conclusion, these results suggest that WZYZ activates the Akt pathway and inhibits the NF-κB pathway by acting on the upstream regulators, thereby improving spermatogenesis deficit induced by THS.
Su-Qin Hu, Dian-Long Liu, Chun-Rui Li, Ya-Hui Xu, Ke Hu, Li-Dan Cui, Jian Guo

2205 related Products with: Wuzi-Yanzong prescription alleviates spermatogenesis disorder induced by heat stress dependent on Akt, NF-κB signaling pathway.

2 Pieces/Box2 Pieces/Box2 Pieces/Box2 Pieces/Box1.5x10(6) cells2 Pieces/Box2 Pieces/Box2 Pieces/BoxInhibitors2 Pieces/Box2 Pieces/Box2 Pieces/Box

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#34549837   2021/09/22 To Up

Predictive factors of survival outcomes in first-line therapy for metastatic castration-resistant prostate cancer.

To investigate predictive factors of survival of metastatic castration-resistant prostate cancer patients undergoing first-line treatment with androgen receptor pathway inhibitors or docetaxel.
Masaki Shiota, Leandro Blas, Satoshi Kobayashi, Takashi Matsumoto, Eiji Kashiwagi, Ario Takeuchi, Junichi Inokuchi, Ken-Ichiro Shiga, Akira Yokomizo, Masatoshi Eto

2625 related Products with: Predictive factors of survival outcomes in first-line therapy for metastatic castration-resistant prostate cancer.



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#34549460   2021/09/21 To Up

Androgen and oestrogen receptors in the growing antlers velvet of adult and yearling pampas deer (Ozotoceros bezoarticus) males.

To determine the presence, quantity and distribution of androgen (AR) and oestrogen receptors (ER) in the antler velvet (AV), samples were collected from adult and yearling pampas deer males, as well as skin from the ventrolateral abdominal area (ASK). Samples were analysed with ligand-binding assays for AR and ER activity and processed for AR and ERβ immunohistochemistry. There was more content of AR in adults than in yearling males (p = 0.02), as well as a category and type of tissue interaction (p = 0.03). There was more ER content in adults than in yearling males (p = 0.005) and in the AV than in the skin (p = 0.0001). The AR-positive score (PS) was greater in AV than in ASK in the surface stroma (p = 0.0007). In the intermediate epidermis, the AR PS was greater in adults than in yearling males (p = 0.04) and in the ASK than in the AV (p < 0.0001). There was a male category and type of tissue interaction for AR PS in the sebaceous glands (p = 0.014). The ERβ PS in the surface stroma was greater in ASK than in AV (p = 0.004) and tended to be greater in yearling than in adult males (p = 0.093). The ERβ PS in the intermediate epithelium and the sebaceous glands was greater in adults than in yearlings (p = 0.004 and p = 0.007, respectively). In conclusion, we reported for the first time the presence of AR and ER in the velvet skin of growing antlers in pampas deer males. Therefore, the velvet skin is sensitive to both androgens and oestrogens. Furthermore, the greater content of oestrogen receptors in the velvet of adult males suggests that adults are more sensitive to this hormone than yearlings, and thus, oestrogens have greater importance in velvet activity regulation in adult males.
Alejandro Bielli, Aline Freitas-de-Melo, Patricia Genovese, Matías Villagrán, Celia Tasende, Rodolfo Ungerfeld

2054 related Products with: Androgen and oestrogen receptors in the growing antlers velvet of adult and yearling pampas deer (Ozotoceros bezoarticus) males.

50 ug 100ul100ug100ul200ul100ug100ul50 ug 200ug200ul100ug100ug

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#34549035   2021/09/14 To Up

Profiling of Androgen-Dependent Enhancer RNAs Expression in Human Prostate Tumors: Search for Malignancy Transition Markers.

Although the ability of androgens to promote prostate cancer development has been known for decades, the molecular mechanisms of androgen receptor (AR) signaling in the tumorigenesis remain unclear. Enhancer RNAs (eRNAs) transcribed from strong enhancers, or super-enhancers (SEs), have recently emerged as a novel class of regulatory non-coding RNAs (ncRNAs) that facilitate transcription, including that of androgen target genes, through chromatin looping to position enhancers proximate to the promoters. The aim of this study was to assess androgen-dependent transcription in prostate tumors of eRNAs (designated as KLK3eRNAs) from the SE of the gene encoding the prostate-specific antigen (PSA) protein, a clinical marker of prostate carcinogenesis.
Koichi Nishimura, Jinichi Mori, Takahiro Sawada, Shuhei Nomura, Alexander Kouzmenko, Kaori Yamashita, Yoshiaki Kanemoto, Tomohiro Kurokawa, Akira Hayakawa, Suguru Tokiwa, Michihisa Ochi, Hiroaki Shimmura, Shigeaki Kato

1405 related Products with: Profiling of Androgen-Dependent Enhancer RNAs Expression in Human Prostate Tumors: Search for Malignancy Transition Markers.

100 μg100 μg0.1mg100 μg100 μg100 μg4 Sample Kit100 μg100 μg100 μg4 Membranes/Box100 μg

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#34548474   2021/09/21 To Up

Selective degradation of AR-V7 to overcome castration resistance of prostate cancer.

Androgen receptor splice variant 7 (AR-V7), a form of ligand-independent and constitutively activating variant of androgen receptor (AR), is considered as the key driver to initiate castration-resistant prostate cancer (CRPC). Because AR-V7 lacks ligand-binding domain, the AR-targeted therapies that aim to inactivate AR signaling through disrupting the interaction between AR and androgen are limited in CRPC. Thus, the emergence of AR-V7 has become the greatest challenge for treating CRPC. Targeting protein degradation is a recently proposed novel avenue for cancer treatment. Our previous studies have been shown that the oncoprotein AR-V7 is a substrate of the proteasome. Identifying novel drugs that can trigger the degradation of AR-V7 is therefore critical to cure CRPC. Here we show that nobiletin, a polymethoxylated flavonoid derived from the peel of Citrus fruits, exerts a potent anticancer activity via inducing G0/G1 phase arrest and enhancing the sensitivity of cells to enzalutamide in AR-V7 positive PC cells. Mechanically, we unravel that nobiletin selectively induces proteasomal degradation of AR-V7 (but not AR). This effect relies on its selective inhibition of the interactions between AR-V7 and two deubiquitinases USP14 and USP22. These findings not only enrich our understanding on the mechanism of AR-V7 degradation, but also provide an efficient and druggable target for overcoming CRPC through interfering the stability of AR-V7 mediated by the interaction between AR-V7 and deubiquitinase.
Yuan Liu, Cuifu Yu, Zhenlong Shao, Xiaohong Xia, Tumei Hu, Weiyao Kong, Xiaoyue He, Wenshuang Sun, Yuanfei Deng, Yuning Liao, Hongbiao Huang

1310 related Products with: Selective degradation of AR-V7 to overcome castration resistance of prostate cancer.

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