GPER1 and microRNA: Two Players in Breast Cancer Progression

Breast cancer is the main cause of morbidity and mortality in women worldwide. However, the molecular pathogenesis of breast cancer remains poorly defined due to its heterogeneity. Several studies have reported that G Protein-Coupled Estrogen Receptor 1 (GPER1) plays a crucial role in breast cancer progression, by binding to estrogens or synthetic agonists, like G-1, thus modulating genes involved in diverse biological events, such as cell proliferation, migration, apoptosis, and metastasis. In addition, it has been established that the dysregulation of short sequences of non-coding RNA, named microRNAs (miRNAs), is involved in various pathophysiological conditions, including breast cancer. Recent evidence has indicated that estrogens may regulate miRNA expression and therefore modulate the levels of their target genes, not only through the classical estrogen receptors (ERs), but also activating GPER1 signalling, hence suggesting an alternative molecular pathway involved in breast tumor progression. Here, the current knowledge about GPER1 and miRNA action in breast cancer is recapitulated, reporting recent evidence on the liaison of these two players in triggering breast tumorogenic effects. Elucidating the role of GPER1 and miRNAs in breast cancer might provide new tools for innovative approaches in anti-cancer therapy.     

雌激素的加压毛细管电色谱分析研究

论文基于苯乙烯基功能整体柱,建立了五种环境雌激素的加压毛细管电色谱分析方法,并应用于鱼肉样品分析。实验考察了有机溶剂浓度、酸度、分离电压、盐浓度、流速等条件对五种雌激素分离的影响。在最优条件下,五种环境雌激素在18 min内实现了基线分离,在4.0×10-7-8.0×10-5g/mL范围内线性良好,检测限在0.8×10-7-5×10-7g/mL范围内。该方法应用于鱼肉实际样的测定,获得回收率范围是78.0%-88.5%。效果良好。     

Kappa-Opioid Receptor Blockade Ameliorates Obesity Caused by Estrogen Withdrawal via Promotion of Energy Expenditure through mTOR Pathway

Weight gain is a hallmark of decreased estradiol (E2) levels because of menopause or following surgical ovariectomy (OVX) at younger ages. Of note, this weight gain tends to be around the abdomen, which is frequently associated with impaired metabolic homeostasis and greater cardiovascular risk in both rodents and humans. However, the molecular underpinnings and the neuronal basis for these effects remain to be elucidated. The aim of this study is to elucidate whether the kappa-opioid receptor (k-OR) system is involved in mediating body weight changes associated with E2 withdrawal. Here, we document that body weight gain induced by OVX occurs, at least partially, in a k-OR dependent manner, by modulation of energy expenditure independently of food intake as assessed in Oprk1−/−global KO mice. These effects were also observed following central pharmacological blockade of the k-OR system using the k-OR-selective antagonist PF-04455242 in wild type mice, in which we also observed a decrease in OVX-induced weight gain associated with increased UCP1 positive immunostaining in brown adipose tissue (BAT) and browning of white adipose tissue (WAT). Remarkably, the hypothalamic mTOR pathway plays an important role in regulating weight gain and adiposity in OVX mice. These findings will help to define new therapies to manage metabolic disorders associated with low/null E2 levels based on the modulation of central k-OR signaling.     

基于DSPE-LC-MS/MS法的畜禽产品中雌激素的测定

本研究建立了畜禽产品中雌酮（estrone,E1）、雌二醇（estradiol,E2）、雌三醇（estriol,E3）以及己烯雌酚（diethylstilbestrol,DES）残留量的分散固相萃取（DSPE）-液相色谱-质谱联用（LC-MS/MS）分析测定方法。样品经乙腈沉淀蛋白质,无水Mg SO4去除水分后,以N-丙基乙二胺（PSA）极性吸附剂分散固相萃取净化,最后通过液相色谱质谱联用测定。在畜禽产品中添加不同浓度的雌激素后用该方法的回收率最高可达到96.63%,4种雌激素的检出限（S/N=3）为1.32¹6.52μg/kg。该方法为畜禽产品中雌激素残留的检测提供了可靠的参考依据。      

超高效液相色谱-质谱联用法检测鱼肉中23种性激素残留量

目的采用QuEChERS快速前处理技术,建立鱼肉中23种性激素的超高效液相色谱-串联四极杆质谱(ultra high performance liquid chromatography tandem quadrupole mass spectrometry,UPLC-MS/MS)分析方法。方法鱼肉样品经乙腈提取后,采用QuEChERS快速方法提取、净化,浓缩后的目标物均采用BEH C_(18)分离柱、多反应监测模式(multiple reaction monitoring,MRM)、外标法定量。雄激素和孕激素采用流动相0.1%甲酸水-甲醇分离,电喷雾正离子(electronic spray ion,ESI~+)扫描;雌激素采用乙腈-水为流动相,电喷雾负离子(ESI~-)扫描。结果 23种性激素标准曲线性良好,相关系数(r~2)均大于0.99。方法的回收率范围60.93%～102.1%,相对标准偏差(relative standard deviation,RSD,n=6)小于16.67%,检出限(limit of detection,LOD,S/N=3)为0.0015～0.47μg/kg。结论该方法简单、高效、可靠性强、灵敏度高,可用于鱼肉中的23种性激素的残留量检测。     

Genetic Variants of GPER/GPR30, a Novel Estrogen-Related G Protein Receptor,Are Associated with Human Seminoma

Testicular germ cell tumors (TGCTs) are the most common solid cancers in young men, with an increasing incidence over several years. However, their pathogenesis remains a matter of debate. Some epidemiological data suggest the involvement of both environmental and genetic factors. We reported two distinct effects of estrogens and/or xeno-estrogens on in vitro human seminoma-derived cells proliferation: (1) an antiproliferative effect via a classical estrogen receptor beta-dependent pathway, and (2) a promotive effect via a non-classical membrane G-protein-coupled receptor, GPR30/GPER, which is only overexpressed in seminomas, the most common TGCT. In order to explain this overexpression, we investigated the possible association of polymorphisms in the GPER gene by using allele-specific tetra-primer polymerase chain reaction performed on tissue samples from 150 paraffin-embedded TGCT specimens (131 seminomas, 19 non seminomas). Compared to control population, loss of homozygous ancestral genotype GG in two polymorphisms located in the promoter region of GPER (rs3808350 and rs3808351) was more frequent in seminomas but not in non-seminomas (respectively, OR = 1.960 (1.172–3.277) and 7.000 (2.747–17.840); p < 0.01). These polymorphisms may explain GPER overexpression and represent a genetic factor of susceptibility supporting the contribution of environmental GPER ligands in testicular carcinogenesis.     

Radical-scavenging Activity of Estrogen and Estrogen-like Compounds Using the Induction Period Method

The radical-scavenging activity of estrogens (estrone, 2-hydroxyestradiol), estrogen-like compounds (diethylstilbestrol, DES; bisphenol A, BPA) and the monophenolic compound 2,6-di-t-butyl-4-methoxyphenol (BMP) was investigated using the method of measuring the induction period for polymerization of methyl methacrylate (MMA) initiated by thermal decomposition of 2,2′-azobisisobutyronitrile (AIBN) and benzoyl peroxide (BPO) at 70°C using differential scanning calorimetry (DSC). The stoichiometric factor (n, number of free radicals trapped by one mole of antioxidant moiety) for the AIBN system declined in the order BMP (2.0), 2-hydroxyestradiol (2.0)> DES (1.3) > BPA (1.2) > estrone (0.9), whereas that for the BPO system declined in the order BMP (2.0) >DES (1.9), BPA (1.9) > estrone (1.3) > 2-hydroxyestradiol (0.7). The inhibition rate constant (k_inh × 10⁻³ M⁻¹s⁻¹) for the AIBN system declined in the order estrone (2.2) > BPA (2.0) > DES (1.9) > 2-hydroxyestradiol (1.2) > BMP (1.1), whereas that for the BPO system declined in the order 2-hydroxyestradiol (3.2) > estrone (1.4) > DES (1.2) > BPA (1.0) > BMP (0.9). The radical-scavenging activity for bioactive compounds such as estrogens should be evaluated using these two methods (the n and k_inh) to elucidate the mechanism of a particular reaction. The great difference of the n and k_inh for estrogens between the AIBN and BPO system suggested that their oxidation process is complex.     

16ξ－溴－3－乙酰氧基－17，17－乙二氧撑－1，3，5（10）－雌三烯的制备及其构型的研究

以３－乙酰氧基－１７，１７－乙二氧撑－１，３，５（１０）－雌三烯为原料制备１６ξ－溴－３－乙酰氧基－１７，１７－乙二氧撑－１，３，５（１０）－雌三烯的反应中，采用不同反应条件，得到２种化合物．通过物理方法和化学方法，证明这２种化合物为立体异构体，并确定了它们的构型．     

污水中典型环境雌激素研究进展

针对污水处理过程中环境雌激素(EEs)的存在和迁移转化现象,综述了污水中EEs的来源与危害、污水中典型EEs的分布及其主要处理技术进展,还提出了一些目前尚待研究的关键技术和相关机理,包括污泥中EEs的检测方法有待完善;污水处理不同单元中EEs的去除对比有待深入分析;污泥对EEs的吸附作用机理及影响因素有待系统性的研究。     

液相色谱-质谱法测定塑料食品包装物中11种环境雌激素

采用液相色谱-质谱对塑料食品包装物中11种环境雌激素(雌三醇、双酚A、对壬基酚、对特辛基苯酚、特丁基对苯二酚、苯酚、二丁基甲基酚、己烯雌酚、对苯二酚、邻甲基对苯二酚、17-β-雌二醇)含量进行测定。样品用二氯甲烷溶解、甲醇沉淀后,经C18固相萃取小柱净化,用液相色谱、质谱检测器,对塑料食品包装物中11种环境雌激素的测定可取得满意的结果。该方法样品平均加标回收率为81.40%～111.11%,相对标准偏差为3.9%～9.7%;塑料食品包装物中11种环境雌激素的检出限为0.0075～0.32mg/kg。