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Estrogen Reduction

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https://www.readbyqxmd.com/read/29906493/the-tamoxifen-derivative-ridaifen-b-is-a-high-affinity-selective-cb-2-receptor-inverse-agonist-exhibiting-anti-inflammatory-and-anti-osteoclastogenic-effects
#1
Lirit N Franks, Benjamin M Ford, Toshifumi Fujiwara, Haibo Zhao, Paul L Prather
Selective estrogen receptor modulators (SERMs) target estrogen receptors (ERs) to treat breast cancer and osteoporosis. Several SERMs exhibit anti-cancer activity not related to ERs. To discover novel anti-cancer drugs acting via ER-independent mechanisms, derivatives of the SERM tamoxifen, known as the "ridaifen" compounds, have been developed that exhibit reduced or no ER affinity, while maintaining cytotoxicity. Tamoxifen and other SERMs bind to cannabinoid receptors with moderate affinity. Therefore, ER-independent effects of SERMs might be mediated via cannabinoid receptors...
June 12, 2018: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29902286/association-of-somatic-driver-alterations-with-prognosis-in-postmenopausal-hormone-receptor-positive-her2-negative-early-breast-cancer-a-secondary-analysis-of-the-big-1-98-randomized-clinical-trial
#2
Stephen J Luen, Rebecca Asher, Chee Khoon Lee, Peter Savas, Roswitha Kammler, Patrizia Dell'Orto, Olivia Maria Biasi, David Demanse, Lellean JeBailey, Sinead Dolan, Wolfgang Hackl, Beat Thuerlimann, Giuseppe Viale, Marco Colleoni, Meredith M Regan, Sherene Loi
Importance: A range of somatic driver alterations has been described in estrogen receptor-positive, HER2-negative (ER+/HER2-) early breast cancer (BC); however, the clinical relevance is unknown. Objective: To investigate associations of driver alterations with prognosis and the role of PIK3CA mutations in prediction of benefit associated with endocrine therapy in postmenopausal patients with ER+/HER2- early BC treated with tamoxifen or letrozole. Design, Setting, and Participants: The Breast International Group (BIG) 1-98 trial randomized 8010 postmenopausal patients with hormone receptor-positive, operable, invasive BC to monotherapy with letrozole, tamoxifen, or a sequential strategy for 5 years...
June 14, 2018: JAMA Oncology
https://www.readbyqxmd.com/read/29900692/direct-activation-of-tachykinin-receptors-within-baroreflex-afferent-pathway-and-neurocontrol-of-blood-pressure-regulation
#3
Mei Yuan, Mei-Na Ma, Ting-Yu Wang, Yan Feng, Pei Chen, Chao He, Sijie Liu, Yun-Xia Guo, Yue Wang, Yao Fan, Lu-Qi Wang, Xiao-Qiang E, Guo-Fen Qiao, Bai-Yan Li
AIM: Substance P (SP) causes vasodilation and blood pressure (BP) reduction. However, the involvement of tachykinin receptors (NKRs) within baroreflex afferent pathway in SP-mediated BP regulation is largely unknown. METHODS: Under control and hypertensive condition, NKRs' expressions were evaluated in nodose (NG) and nucleus of tractus solitary (NTS) of male, female, and ovariectomized (OVX) rats; BP was recorded after microinjection of SP and NKRs agonists into NG; Baroreceptor sensitivity (BRS) was tested as well...
June 13, 2018: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/29899696/identification-of-steroidogenic-components-derived-from-gardenia-jasminoides-ellis-potentially-useful-for-treating-postmenopausal-syndrome
#4
Xueyu Wang, Guo-Cai Wang, Jianhui Rong, Shi Wei Wang, Tzi Bun Ng, Yan Bo Zhang, Kai Fai Lee, Lin Zheng, Hei-Kiu Wong, Ken Kin Lam Yung, Stephen Cho Wing Sze
Estrogen-stimulating principles have been demonstrated to relieve postmenopausal syndrome effectively. Gardenia jasminoides Ellis (GJE) is an herbal medicine possessing multiple pharmacological effects on human health with low toxicity. However, the therapeutic effects of GJE on the management of postmenopausal syndrome and its mechanism of action have not been fully elucidated. In this study, network pharmacology-based approaches were employed to examine steroidogenesis under the influence of GJE. In addition, the possibility of toxicity of GJE was ruled out and four probable active compounds were predicted...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29897771/in-situ-click-reaction-coupled-with-quantitative-proteomics-for-identifying-protein-targets-of-catechol-estrogens
#5
Huei-Chen Liang, Yi-Chen Liu, Hsin Chen, Ming Chun Ku, Quynh-Trang Do, Chih-Yen Wang, Shun-Fen Tzeng, Shu-Hui Chen
Catechol estrogens (CEs) are metabolic electrophiles that actively undergo covalent interaction with cellular proteins, influencing molecular function. There is no feasible method to identify their binders in a living system. Herein, we developed a click chemistry-based approach using ethinylestradiol (EE2) as the precursor probe coupled with quantitative proteomics to identify protein targets of CEs and classify their binding strengths. Using in-situ metabolic conversion and click reaction in liver microsomes, CEs-protein complex was captured by the probe, digested by trypsin, stable isotope labeled via reductive amination, and analyzed by liquid chromatography-mass spectrometry (LC-MS)...
June 13, 2018: Journal of Proteome Research
https://www.readbyqxmd.com/read/29889977/ovulation-induction-in-polycystic-ovary-syndrome
#6
Tom Tanbo, Jan Mellembakken, Sverre Bjercke, Eva Ring, Thomas Åbyholm, Peter Fedorcsak
The objective of this narrative review is to suggest a rational order of treatment choices in anovulatory women with polycystic ovary syndrome (PCOS), for whom a multitude of treatment options exist. In obese/overweight PCOS patients the importance of weight reduction should be stressed. Inositol, a dietary supplement with a documented effect on ovulation and without side effects in the doses recommended, may be suggested. Additional first line medical alternatives include insulin sensitizers, selective estrogen receptor modulators and aromatase inhibitors...
June 11, 2018: Acta Obstetricia et Gynecologica Scandinavica
https://www.readbyqxmd.com/read/29889764/long-term-outcomes-of-elagolix-in-women-with-endometriosis-results-from-two-extension-studies
#7
Eric Surrey, Hugh S Taylor, Linda Giudice, Bruce A Lessey, Mauricio S Abrao, David F Archer, Michael P Diamond, Neil P Johnson, Nelson B Watts, J Chris Gallagher, James A Simon, Bruce R Carr, W Paul Dmowski, Nicholas Leyland, Sukhbir S Singh, Tomasz Rechberger, Sanjay K Agarwal, W Rachel Duan, Brittany Schwefel, James W Thomas, Paul M Peloso, Juki Ng, Ahmed M Soliman, Kristof Chwalisz
OBJECTIVE: To evaluate the efficacy and safety of elagolix, an oral, nonpeptide gonadotropin-releasing hormone antagonist, over 12 months in women with endometriosis-associated pain. METHODS: Elaris Endometriosis (EM)-III and -IV were extension studies that evaluated an additional 6 months of treatment after two 6-month, double-blind, placebo-controlled phase 3 trials (12 continuous treatment months) with two elagolix doses (150 mg once daily and 200 mg twice daily)...
June 6, 2018: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/29877575/brca1-associated-mammary-tumorigenesis-is-dependent-on-estrogen-rather-than-progesterone-signaling
#8
Marieke van de Ven, Xiaoling Liu, Eline van der Burg, Sjoerd Klarenbeek, Xanthippi Alexi, Wilbert Zwart, Fred Dijcks, Peter Bouwman, Jos Jonkers
Hereditary breast cancers in BRCA1-mutation carriers are mostly estrogen receptor alpha (ERα) and progesterone receptor (PR) negative, however, hormone depletion via bilateral oophorectomy does result in a marked reduction of breast cancer risk, suggesting that BRCA1-associated breast tumorigenesis is dependent on hormone signaling. We used genetically engineered mouse models to dissect the individual influences of ERα and PR signaling in the development of BRCA1-deficient breast cancer. In line with the human data, BRCA1-deficient mouse mammary tumors are ERα-negative and bilateral ovariectomy leads to abrogation of mammary tumor development...
June 7, 2018: Journal of Pathology
https://www.readbyqxmd.com/read/29867564/notch1-mediates-preconditioning-protection-induced-by-gper-in-normotensive-and-hypertensive-female-rat-hearts
#9
Carmine Rocca, Saveria Femminò, Giorgio Aquila, Maria C Granieri, Ernestina M De Francesco, Teresa Pasqua, Damiano C Rigiracciolo, Francesca Fortini, Maria C Cerra, Marcello Maggiolini, Pasquale Pagliaro, Paola Rizzo, Tommaso Angelone, Claudia Penna
G protein-coupled estrogen receptor (GPER) is an estrogen receptor expressed in the cardiovascular system. G1, a selective GPER ligand, exerts cardiovascular effects through activation of the PI3K-Akt pathway and Notch signaling in normotensive animals. Here, we investigated whether the G1/GPER interaction is involved in the limitation of infarct size, and improvement of post-ischemic contractile function in female spontaneous hypertensive rat (SHR) hearts. In this model, we also studied Notch signaling and key components of survival pathway, namely PI3K-Akt, nitric oxide synthase (NOS) and mitochondrial K+ -ATP (MitoKATP) channels...
2018: Frontiers in Physiology
https://www.readbyqxmd.com/read/29858695/hormones-removal-from-municipal-wastewater-using-ultrasound
#10
Aliakbar Roudbari, Mashallah Rezakazemi
Estrogens are one of the micro-pollutants in the wastewater which have detrimental effects on water living organisms. The aim of this study was to evaluate the efficiency of ultrasound to reduce the estrogen (E1) and 17 beta-estradiol (E2) from municipal wastewater. Hence, a cylindrical batch reactor was designed. The effects of powers, frequency, exposure time and pH on reduction efficiency were investigated. The residual concentration of E1 and E2 hormones was measured in reactor effluent by electrochemiluminescence (ECL) method...
June 1, 2018: AMB Express
https://www.readbyqxmd.com/read/29846718/a-ternary-mixture-of-common-chemicals-perturbs-benign-human-breast-epithelial-cells-more-than-the-same-chemicals-do-individually
#11
Shanaz H Dairkee, Gloria Luciani-Torres, Dan H Moore, Ian M Jaffee, William H Goodson
As a continuous source of hormonal stimulation, environmentally ubiquitous estrogenic chemicals, i.e. xenoestrogens (XEs), are a potential risk factor for breast carcinogenesis. Given their wide distribution in the environment and the fact that bisphenol-A (BPA), methylparaben (MP), and perfluorooctanoic acid (PFOA) are uniformly detected in unselected body fluid samples, it must be assumed that humans are simultaneously exposed to these chemicals almost daily. We studied the effects of a ternary mixture of BPA, MP, and PFOA on benign breast epithelial cells at the range of concentrations observed for single chemicals in human samples...
May 28, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/29803894/impact-of-selective-serotonin-reuptake-inhibitors-ssris-during-pregnancy-and-lactation-a-focus-on-short-and-long-term-vascular-effects
#12
REVIEW
S Zullino, T Simoncini
SSRIs are the first choice for the treatment of mood disorders during pregnancy and lactation. Despite the known side effects, the benefits/risks balance suggests their use. Hypertensive disorders of pregnancy (HDP) and Intrauterine growth restriction (IUGR) are the main vascular effects of these drugs, with mechanisms that involves endothelial dysfunction in feto-placental system. These data are supported by animal models, even if preliminary findings are not yet adequately supported by molecular and clinical data...
May 24, 2018: Vascular Pharmacology
https://www.readbyqxmd.com/read/29801469/analysis-of-the-pvuii-and-xbai-polymorphisms-in-the-estrogen-receptor-alpha-gene-in-girls-with-central-precocious-puberty-a-pilot-study
#13
José Maria Soares-Jr, Felisbela Soares de Holanda, Cézar Noboru Matsuzaki, Isabel Cristina Esposito Sorpreso, Eduardo Carvalho de Arruda Veiga, Luiz Carlos de Abreu, Kátia Cândido Carvalho, Edmund Chada Baracat
BACKGROUND: Precocious puberty (PP) is defined as premature pubertal development. Its consequences surpass the physical evidence of sexual maturity with the premature epiphyseal closure of the long bones and the reduction of adult stature by varied degrees. Central PP is characteristically dependent on GnRH and most of its causes are not completely known. Altered estrogen action is also believed to be involved in the genesis of PP. In fact, estrogen receptor alpha (Rea) gene polymorphisms may be associated with early age at menarche...
May 25, 2018: BMC Medical Genetics
https://www.readbyqxmd.com/read/29790381/what-do-tsecs-provide-in-the-menopausal-hormone-therapy
#14
Placido Llaneza, Joaquim Calaf, Ana Rosa Jurado, Nicolas Mendoza, Borja Otero, Francisco Quereda, Rafael Sánchez-Borrego, Daniel Lubian
Tissue-selective estrogen complex (TSEC) is projected as a progestogen-free option for the treatment of estrogen deficiency symptoms in postmenopausal, non-hysterectomized women. TSEC combines the benefits of estrogen with a selective estrogen receptor modulator (SERM), in this case bazedoxifene acetate (BZA), which has an antagonistic effect on the endometrium, thus avoiding the use of progestins. The authorized TSEC combination (conjugated estrogens [CE] 0.45 mg/BZA 20 mg) for the alleviation of vasomotor symptoms has been demonstrated in randomized clinical trials compared with placebo or menopausal hormone therapy (MHT)...
May 23, 2018: Gynecological Endocrinology
https://www.readbyqxmd.com/read/29783074/fsh-receptor-binding-inhibitor-restrains-follicular-development-and-possibly-attenuates-carcinogenesis-of-ovarian-cancer-through-down-regulating-expression-levels-of-fshr-and-er%C3%AE-in-normal-ovarian-tissues
#15
Gong Zhuandi, Che Tuanjie, Lai Luju, Ayimuguli Abdiryim, Deng Yingying, Liang Haoqin, Wei Suocheng, Ding Li
OBJECTIVES: The current study aimed to investigate FSH receptor binding inhibitor (FRBI) effects in the expressions of FSH receptor (FSHR) and estrogen receptor-beta (ERβ) in the mice ovaries at the gene and protein levels, also to find the potential efficacy of FRBI on suppressing ovarian cancer through down-regulating over-expression of FSHR and ERβ in the normal ovarian tissues. METHODS: 180 female mice were randomized into six groups (n = 30). Mice of FRBI-1, FRBI-2 and FRBI-3, FRBI-4 were intramuscularly injected with FRBI of 10, 20, 30 and 40 mg/kg, respectively, for five consecutive days...
May 18, 2018: Gene
https://www.readbyqxmd.com/read/29781507/effect-of-estradiol-on-fibroblasts-from-postmenopausal-idiopathic-carpal-tunnel-syndrome-patients
#16
Yoshiaki Yamanaka, Kunitaka Menuki, Takafumi Tajima, Yasuaki Okada, Kenji Kosugi, Yukichi Zenke, Akinori Sakai
Fibrosis of the subsynovial connective tissue (SSCT) is a characteristic finding in patients with idiopathic carpal tunnel syndrome (CTS). Idiopathic CTS frequently occurs in postmenopausal women; therefore, female steroid hormones, especially estrogens, may be involved in its development. In this study, we evaluated the effect of the estradiol on the expression of genes and proteins related to fibrosis of SSCT fibroblasts from patients with idiopathic CTS. This study included 10 postmenopausal women (mean age 76 years)...
May 21, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29781132/egr2-mediates-the-differentiation-of-mouse-uterine-stromal-cells-responsiveness-to-hb-egf-during-decidualization
#17
Liang Yue, Hai-Fan Yu, Zhan-Qing Yang, Xue-Chao Tian, Lian-Wen Zheng, Bin Guo
Although Egr2 is involved in regulating the folliculogenesis and ovulation, there is almost no data describing its physiological function in embryo implantation and decidualization. Here, we showed that Egr2 mRNA was distinctly accumulated in subluminal stromal cells around implanting blastocyst on day 5 of pregnancy as well as in estrogen-activated implantation uterus. Estrogen induced the expression of Egr2 in uterine epithelia. Elevated expression of Egr2 mRNA was also observed in the decidual cells. Silencing of Egr2 by specific siRNA weakened the proliferation of uterine stromal cells and reduced the expression of Ccnd1, Ccnd3, Cdk4, and Cdk6...
May 20, 2018: Journal of Experimental Zoology. Part B, Molecular and Developmental Evolution
https://www.readbyqxmd.com/read/29777335/a-trisubstituted-pyrazole-derivative-reduces-dmba-induced-mammary-tumor-growth-in-rats-by-inhibiting-estrogen-receptor-%C3%AE-expression
#18
Hanumappa Ananda, Kothanahally S Sharath Kumar, Muddenahalli S Sudhanva, Shobith Rangappa, Kanchugarakoppal S Rangappa
Aberrant expression of estrogen receptor alpha (ER-α) is observed in many pathological complications like breast cancer, endometrial cancer, and in osteoporosis. ER-α plays a vital role in the initiation and progression of breast cancer and confers chemo and radioresistance to the cancer cells by upregulating expression of anti-apoptotic proteins. The synthetic pyrazole derivative 3-(1-(4-bromophenyl)-5-phenyl-1H-pyrazol-3-yl)pyridine (compound 5d) displays significant cytotoxicity against mammary carcinoma cells...
May 18, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29772574/is-there-a-rationale-behind-pharmacotherapy-in-idiopathic-gynecomastia
#19
Anna Kasielska-Trojan, Marian Danilewicz, Bogusław Antoszewski
BACKGROUND/AIMS: The aim of this research was to analyze digit ratio in relation to estrogen receptor (ER) and progesterone receptor (PR) expression and to verify digit ratio (2D: 4D) as a marker of ER and PR overexpression in the male breast. METHODS: This study included 35 patients who underwent breast reduction due to the idiopathic form of gynecomastia. The average age of the studied individuals was 25.7 years (SD = 7.8). ER and PR expression was detected in breasts, and digit ratios were calculated in patients with idiopathic gynecomastia...
May 17, 2018: Hormone Research in Pædiatrics
https://www.readbyqxmd.com/read/29766363/palbociclib-in-highly-pretreated-metastatic-er-positive-her2-negative-breast-cancer
#20
G Hoste, K Punie, H Wildiers, B Beuselinck, I Lefever, E Van Nieuwenhuysen, S N Han, P Berteloot, N Concin, R Salihi, I Vergote, P Neven
PURPOSE: We aimed to investigate the role of palbociclib, a first-in-class cyclin-dependent kinase 4 and 6 inhibitor, in postmenopausal women with highly pretreated endocrine therapy-resistant metastatic breast cancer (MBC). METHODS: Between 28 September 2015 and 14 March 2017, a compassionate use program was established in the University Hospitals Leuven in which 82 postmenopausal women with estrogen receptor-positive, HER2-negative MBC were included after at least four lines of systemic treatment...
May 16, 2018: Breast Cancer Research and Treatment
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