肥胖因子三丁基锡影响细胞代谢功能的研究进展

肥胖是诸多心、脑血管疾病和代谢性疾病的危险因素。近年来随着全球肥胖人数的快速增加,肥胖现已成为重要的公共卫生问题之一。肥胖除了与遗传、能量摄入过量、缺乏运动等因素有关外,许多环境内分泌干扰物在肥胖发生的过程中也起了重要的作用。在诸多的内分泌干扰物中,三丁基锡是最早被认定为属于肥胖因子(obesogen)范畴的一种化合物,它能够通过促进脂肪堆积、干扰激素分泌等途径导致肥胖的发生。该文对三丁基锡干扰细胞代谢,促进肥胖发生的主要方式及机制进行综述。     

镉的环境激素效应研究进展

镉属于环境内分泌干扰物,具有激素效应,可以模拟体内正常的激素水平。根据近年来关于镉的激素效应的研究报道,从镉的激素作用机理及其诱导肿瘤等方面综述了镉的激素效应。     

环境雌激素双酚A的研究进展

环境荷尔蒙是现代生命科学领域研究的热点之一,如今越来越多的人开始关注这一话题。在我们的生活环境中充斥着各种化学有毒试剂,其中,有一类物质能够模拟或抑制内分泌激素的活动,我们称之为内分泌干扰物。内分泌干扰物有能力改变内分泌系统的结构和功能。双酚A作为一种环境雌激素,属于内分泌干扰物的一种。双酚A被广泛应用于聚碳酸酯塑料和环氧树脂的制造。双酚A具有弱雌激素效应,能够与雌激素受体结合,引起内分泌系统的应答。目前的研究表明,双酚A会透过血胎屏障影响到胚胎发育,会对神经内分泌系统、肝组织功能以及生殖器的发育造成损伤。本文主要综述了环境雌激素双酚A在小鼠发育阶段所引起的诸多不利影响,并对环境荷尔蒙未来的研究方向进行了展望。     

环境内分泌干扰物对基因甲基化的影响

环境内分泌干扰物广泛地存在于人类的生存环境中,大多数具有显著的生殖毒性,不仅影响胚胎神经系统及生殖系统的发育,并可有传代效应及致癌作用.研究表明,环境内分泌干扰物大多是通过表观遗传学机制发挥其毒性作用. 目前,此方面的研究主要集中在胎儿及新生儿期暴露于内分泌干扰物对机体基因甲基化修饰的改变方面.本文就环境内分泌干扰物对胚胎发育的影响,及其传代效应和致癌作用在基因甲基化修饰调控方面作一综述.     

环境激素对人类健康的危害及其作用机制

环境激素是环境中的激素类似物,它在人体和动物体内发挥着类似于激素的作用,通常称为＂外因性内分泌干扰物质＂,干扰体内正常激素的作用.该文介绍激素与环境激素的区别、环境激素的特性、种类;重点阐述环境激素的及其内分泌干扰机制;从环境激素对人类的健康,尤其是对生殖健康的危害,提出了防治环境激素污染的措施.     

二恶英对雌激素受体的干扰作用

核受体相关的肿瘤,如乳腺癌和前列腺癌的发生、发展主要依赖于性激素的分泌。环境内分泌干扰物如Ⅲ二恶英,可作为雌激素受体的诱导配体,直接或间接地与转录因子相互作用,从而干扰基因的转录。此外,二恶英还能使雌激素受体发生泛素化修饰,促进它的降解,并使雌激素依赖性的基因转录受到抑制,成为内分泌干扰因子。本文综述了二恶英的类雌激素效应、致癌性以及激素信号干扰的最新研究进展。     

环境激素浅说

１　环境激素的概念动物激素是动物的内分泌腺分泌的,通过体液运送到身体的特定作用部位,对生物的新陈代谢、生长发育等生命活动起重要调节作用的微量有机化合物。但据最近的观察和研究表明,许多种类的人工合成的化学物质,均能影响和扰乱生物体内固有的内分泌系统,导致内分泌障碍,我们称这类环境中的内分泌干扰物为环境激素。２　环境激素的种类根据“世界自然保护基金会”的调查,目前,人们已知晓的环境激素多达７２种,主要存在于二恶英类物质和人工合成的各种化学物质内,并散布于人类的生活环境中。二恶英是以两个氧原子桥结合两…     

环境雄激素的危害、来源与环境行为

内分泌干扰物(EDCs)因低剂量即可导致严重的生理效应而成为研究的热点,环境雄激素就是典型的内分泌干扰物之一,它主要来源于畜禽粪尿的排放以及造纸厂和城市污水处理厂处理不彻底的废水排放,污染源的连续性排放致使环境雄激素物质在各类环境介质中被不断检出,并导致一些地区出现鱼类的雄性化现象,对环境健康和生态安全构成严重威胁。综述了环境雄激素的暴露危害、主要来源以及环境雄激素在不同环境中的浓度水平和分布特征,介绍了环境雄激素的分析检测手段,阐述了环境雄激素在环境中的迁移、吸附、降解等过程,并对环境雄激素的研究进行了展望。     

双酚A对雄性生殖系统毒性的实验进展与机制研究

环境雌激素双酚A(BPA)作为作为一种内分泌干扰物,双酚A对雄性生殖系统的毒性作用逐渐引起人们的重视。实验发现,其对睾丸组织细胞,雄性生殖器官和生殖激素均有影响,致突变的毒性机制也有多种理论假设,本文就双酚A对雄性生殖系统毒性作用进行综述,以期为进一步的理论研究提供依据。     

外因性内分泌干扰物质对人类的危害及预防

论述了外因性内分泌干扰物质是环境中的激素类似物,它能通过与激素受体结合,干扰正常的生理代谢、内分泌、生殖机能,引起种种负面的生物学效应,同时提出了对外因性内分泌干扰物质的控制和预防措施。     

Developmental exposure to low-dose estrogenic endocrine disruptors alters sex differences in exploration and emotional responses in mice

Estrogenic endocrine disruptors (EEDs) are naturally occurring or man-made compounds present in the environment that are able to bind to estrogen receptors and interfere with normal cellular development in target organs and tissues. There is mounting evidence that EEDs can interfere with the processes of sexual differentiation of brain and behavior in different animal models. We investigated the effects of maternal exposure to EEDs, at concentrations within the range of human exposure and not patently teratogenic, on behavioral responses of male and female house mice (Mus musculus domesticus) before and after puberty. Pregnant dams were trained to spontaneously drink daily doses of corn oil with or without the estrogenic plastic derivative, bisphenol A (BPA 10 microg/kg), or the estrogenic insecticide methoxychlor (MXC 20 microg/kg) from gestation day 11 to postpartum day 8. Their male and female offspring were examined at different ages to examine several components of explorative and emotional behaviors in 3 experimental paradigms: a novelty test before puberty and, as adults, a free-exploratory open-field test and the elevated plus maze test. The main results are sex differences in control mice on a number of behavioral responses at both ages and in all experimental paradigms, while perinatal exposure to BPA or MXC decreased or eliminated such sex differences. The present findings are evidence of long-term consequences of developmental exposure to BPA and MXC on neurobehavioral development and suggest a differential effect of low-dose exposure to these estrogenic chemicals in males and females.     

GPR30, the non-classical membrane G protein related estrogen receptor, is overexpressed in human seminoma and promotes seminoma cell proliferation

Background

Testicular germ cell tumours are the most frequent cancer of young men with an increasing incidence all over the world. Pathogenesis and reasons of this increase remain unknown but epidemiological and clinical data have suggested that fetal exposure to environmental endocrine disruptors (EEDs) with estrogenic effects, could participate to testicular germ cell carcinogenesis. However, these EEDs (like bisphenol A) are often weak ligands for classical nuclear estrogen receptors. Several research groups recently showed that the non classical membrane G-protein coupled estrogen receptor (GPER/GPR30) mediates the effects of estrogens and several xenoestrogens through rapid non genomic activation of signal transduction pathways in various human estrogen dependent cancer cells (breast, ovary, endometrium). The aim of this study was to demonstrate that GPER was overexpressed in testicular tumours and was able to trigger JKT-1 seminoma cell proliferation.

Results

We report here for the first time a complete morphological and functional characterization of GPER in normal and malignant human testicular germ cells. In normal adult human testes, GPER was expressed by somatic (Sertoli cells) and germ cells (spermatogonia and spermatocytes). GPER was exclusively overexpressed in seminomas, the most frequent testicular germ cell cancer, localized at the cell membrane and triggered a proliferative effect on JKT-1 cells in vitro, which was completely abolished by G15 (a GPER selective antagonist) and by siRNA invalidation.

Conclusion

These results demonstrate that GPER is expressed by human normal adult testicular germ cells, specifically overexpressed in seminoma tumours and able to trigger seminoma cell proliferation in vitro. It should therefore be considered rather than classical ERs when xeno-estrogens or other endocrine disruptors are assessed in testicular germ cell cancers. It may also represent a prognosis marker and/or a therapeutic target for seminomas.     

Perturbateurs endocriniens environnementaux et cancers hormonodépendants. De nouveaux facteurs de risque ?

The involvement of environmental endocrine disruptors (EED) in hormone dependent carcinogenesis is supported by: (1) in utero exposure to distilbene, a human experimental model which led to vaginal adenocarcinoma in the young daughter and an increased risk of breast cancer after 40 years; (2) epidemiological case/control studies showing although many confounders and methodological biais, a correlation between blood, adipose tissue or tumoral EED levels and hormone dependent cancers (breast cancer and PCB, PAH and dioxine levels; prostate cancer and chlordecone levels; testicular germ cell cancer and of PCB, HCB or chlordane blood levels of the mothers); (3) experimental models able to induce in rodents after fetal or perinatal exposure to diéthylstilbestrol (DES), bisphenol A or atrazine, adult breast or prostate cancers; (4) in vitro malignant cell studies showing how EEDs like bisphenol A are able to interfere with prostate, breast or testicular germ cell proliferation, apoptosis and survey. All these reports suggest a reassessment of EED chemotoxicity during carcinogenesis which needs to include low doses of EEDs with additive or synergistic mixture during critical windows of exposure such as fetal or perinatal periods leading to stable epigenetic modifications which do not change the genetic code but may participate to the malignant transformation and/or promotion.     

An arming yeast with the ability to entrap fluorescent 17beta-estradiol on the cell surface

We constructed a novel surface-engineered yeast displaying the ligand-binding domain of the rat estrogen receptor (ERLBD). ERLBD, display of which on the yeast cell surface was confirmed by immunofluorescence, possessed strong binding activity to fluorescent 17beta-estradiol - an analogue of the natural ligand of the estrogen receptor - that was comparable to the activity of the native receptor. Environmental homeostasis has recently been disturbed by endocrine disruptors, which cause confusion in the hormone secretion system. It is therefore very important to identify chemical compounds with hormone-like activity and remove them from the environment. The present results demonstrate that the new arming yeast displaying ERLBD on its cell surface will be capable of screening, entrapping, and removing estradiol-like compounds from the environment.     

环境激素类物质对人类健康的影响

环境激素是具有生物体内分泌激素干扰作用的一大类化学物质。环境激素在环境中普遍存在,不仅对生物的繁殖具有一定影响,而且还对生物的许多行为和感知能力产生影响。论文综述了近年来国内外有关环境激素的研究进展,综合分析了环境激素对人类健康的影响,阐述了其作用机理,并探讨了环境激素类物质控制和管理途径。     

Methoprene Photolytic Compounds Disrupt Zebrafish Development,Producing Phenocopies of Mutants in the Sonic Hedgehog Signaling Pathway

Environmental chemicals have been proposed to impact endocrine or retinoid pathways, causing developmental abnormalities in humans and other vertebrates. Presented evidence shows that exposure of zebrafish embryos to sunlight-induced photolytic products of the pesticide methoprene results in developmental defects in the head, heart, pectoral fins, and somites, and in spinal motor and optic nerve axons. Exposed embryos are phenocopies of zebrafish you-type mutants and, as in the mutant sonic-you, show underexpression of the signaling protein sonic hedgehog. Reduced expression of sonic hedgehog is also displayed in embryos treated with the retinoic acid synthesis inhibitor citral. This study identifies citral-related compounds as embryonic signaling disruptors of potential environmental concern.     

Xenoestrogenic compounds promote capacitation and an acrosome reaction in porcine sperm

There is growing evidence that endocrine disruptors bind to hormone receptors; since these receptors are present on the sperm membrane, sperm are potentially a useful model for examining estrogenic activities of endocrine disruptors. The objective of the present study was to compare the effects of two xenoestrogenic compounds (genistein and 4-tert-octylphenol) to those of two steroids (estrogen and progesterone) and heparin on in vitro capacitation and the acrosome reaction in a porcine sperm model. Porcine sperm were incubated with various concentrations (0.001-100 μM) of each chemical for 15 or 30 min, and then capacitation and the acrosome reaction were assessed using chlortetracycline. Estrogen and progesterone were considerably more potent than the other chemicals in stimulating capacitation. Estrogen stimulated sperm capacitation at all tested concentrations after 15 min of incubation (P < 0.05), whereas progesterone stimulated sperm capacitation at all tested concentrations after 15 and 30 min (P < 0.05). The effect of genistein on sperm capacitation was comparable with that of estrogen, and it was the most potent in stimulating the acrosome reaction. Genistein stimulated the acrosome reaction at all tested concentrations after 30 min (P < 0.05). However, 4-tert-octylphenol had the least effect on capacitation and the acrosome reaction. In summary, since all chemicals studied effectively altered capacitation and the acrosome reaction, it was concluded that porcine sperm could be a useful model for in vitro screening of potential endocrine disruptors. It was noteworthy that concurrent comparisons to steroids increased the ability to determine estrogenic characteristics of the tested chemicals.     

A treatise on hazards of endocrine disruptors and tool to evaluate them

Hormones mediate a major part of our essential physiological functions. Both endogenous and exogenous compounds and their metabolites are known to act through hormone receptors leading to regulation of endocrine function. The endogenous ligands that control reproductive functions are generally steroids such as 17beta-estradiol, androgens, progesterone, pregnenolone and glucocorticoids. However, exogenous compounds that are structurally and functionally similar gain entry into animals including humans through the diet or by occupational exposures, causing endocrine disruption. In the recent decade, there is a lot of apprehension about the so-called "endocrine disruptors" which are wide spread in the environment, mainly due to unrestricted human activity. These compounds of anthropogenic or natural origin mimic the action of sex hormones and can interfere with the endocrine system. It has been hypothesized that environmental exposure to synthetic estrogenic chemicals and related endocrine active compounds may be responsible for malformations in the male reproductive tract, crytorchidism, hypospadias, decrease in sperm counts, decreased male reproductive capacity and even testicular cancers. The increasing concern in both public and scientific communities about these abnormalities have prompted the initiation of epidemiological studies to not only identify, but to also analyze the short and long term effects of endocrine disruptors. As a result, a number of assays have been developed and are undergoing validation aimed at high throughput screening of chemical agents that disrupt endocrine activity. This review consolidates the findings of epidemiological studies, particularly in relation to male reproductive disorders and brings to light the various types of in vitro and in vivo models that are available for tiered testing of suspected compounds.