骨骼肌芳香化酶的研究进展

芳香化酶是机体雌激素合成的限速酶之一,在调节机体雌激素平衡方面发挥着重要作用。近年来研究发现,骨骼肌内也存在芳香化酶的表达和雌激素的生成,并有研究提示雌激素水平的下降导致了骨骼肌雌激素受体和骨骼肌质量的下降。然而调控芳香化酶的水平,是否可以减缓由雌激素分泌量减少导致的肌肉减少症,还没有定论。本综述在介绍芳香化酶结构和催化机制的基础上,探讨芳香化酶、雌激素、骨骼肌三者的作用关系,旨在探究芳香化酶和雌激素对维持骨骼肌健康的作用。     

畜禽养殖过程中雌激素的排放及其环境行为

由于存在广泛和较强的内分泌干扰性,环境雌激素越来越受到关注,其中人与动物排放的天然类固醇雌激素(雌酮、雌二醇和雌三醇)具有最强的干扰性。综述了畜禽养殖过程中天然雌激素的排放、危害以及其物化性质,并结合国内外近期研究阐明了天然雌激素的吸附、降解和迁移转化等环境行为。在目前雌激素研究现状的基础上,对未来的研究方向及目标提出了建议。     

环境雌激素双酚A对脑和行为发育的影响

双酚A是一种具有代表性的环境内分泌干扰物, 其广泛使用引起的对人类和野生动物的危害不容忽视. 双酚A具有类雌激素和抗雌激素活性, 可与雌激素受体结合, 模拟或干扰体内雌激素的合成、代谢和活动, 从而影响机体的生理功能. 在脑发育过程中, 双酚A不仅影响脑内雌激素合成关键酶芳香化酶的表达和活性, 还可改变不同脑区雌激素受体(ERα和ERβ)的表达, 并因此放大或干扰雌激素对脑发育的调节作用. 经典的雌激素核受体机制和非基因组细胞信号系统均参与双酚A对脑发育的影响. 许多脑区特别是与行为相关的如下丘脑、脑干蓝斑、皮层和海马等脑区的结构、递质系统等发育受双酚A影响, 干扰其发育的性别分化, 并因此影响生殖行为、探究、焦虑和学习记忆等多种神经行为的性别分化. 双酚A影响脑发育的细胞、脑区和时间特异性, 以及对脑发育过程影响的动态变化, 使双酚A对脑发育的影响非常复杂. 发育中的脑对双酚A特别敏感, 低于环境排放安全标准剂量的双酚A已可影响脑和行为的发育. 因此, 双酚A环境排放安全标准的重新制定非常必要, 而对双酚A毒理学的进一步实验研究和流行病学研究将有助于其环境排放安全新标准的确定.     

环境雌激素生态影响的研究进展

环境雌激素(ｅｃｏｅｓｔｒｏｇｅｎ) ,是指能够扰乱动物内分泌活动 ,生理活性与雌激素较为相似的动物体外化学物质 ,包括人工合成化合物以及植物天然雌激素 ,由于目前所发现的干扰动物及人体内分泌系统的有机化合物绝大多数都具有激素特征 ,因此通常又将环境激素称做“干扰内分泌化合物”(ｅｎｄｏｃｒｉｎｅｄｉｓｒｕｐｔｉｎｇｃｈｅｍｉ ｃａｌｓ或ｅｎｄｏｃｒｉｎｅｄｉｓｒｕｐｔｅｒｓ)。环境激素问题只是在最近几年才引起世界关注 ,但由于环境激素污染范围广、影响大 ,对人类生存的威胁更直接 ,目前 ,西方国家将环境激素问题与臭…     

低剂量双酚A灌胃对去卵巢小鼠子宫的增生作用

目的观察小鼠经消化道途径给予低剂量环境内分泌干扰物双酚A对子宫的作用及机制。方法雌性ICR小鼠切除双侧卵巢,恢复性饲养1周,剔除异常个体后,50只动物随机分成5组,每组10只动物,依次皮下注射(sc)10.0μg/(kg·d)17β-雌二醇,灌胃(ig)0、20.0、60.0和180.0μg/(kg·d)BPA,连续7d。动物每3d称量体重一次,于最后一次给药24h后,阴道涂片检测角化上皮细胞,颈椎脱臼处死动物,取子宫,称其干湿重,计算子宫脏器指数,组织切片,HE染色后利用图像分析系统测量子宫上皮高度和宫腔面积。免疫组化法分析子宫雌激素受体(ER)和孕激素受体(PR)表达。结果①与对照组相比,雌二醇和BPA低剂量组动物体重增加,BPA中高剂量组动物体重无明显差异。②阴道涂片结果显示,处于动情期动物数分别为:对照组0/10,雌二醇组10/10,BPA低剂量组2/10,BPA中剂量组1/10,BPA高剂量组0/10;③BPA低剂量组动物子宫湿重和含水量较对照组增加,脏器系数增大,BPA中高剂量组子宫湿重和脏器系数较对照组降低明显(P0.05);④病理组织学及显微图像分析结果显示,BPA低剂量组动物子宫腔面积较对照组增大,中高剂量组子宫腔面积明显减小(P0.01);低剂量组动物子宫上皮高度较对照组增高(P0.01),中高剂量组子宫上皮高度降低明显(P0.01)。⑤免疫组化结果显示,低剂量BPA能增强小鼠子宫ER和PR表达,但随剂量增加,ER表达下降。结论BPA经消化道途径给予ICR小鼠,人环境暴露剂量下具有雌激素活性,但雌激素活性随BPA剂量增大呈现下降趋势。     

部分水产养殖动物性别控制基因的研究进展

动物的性别是受遗传或环境等因素控制的。自从在哺乳动物中发现了性别决定基因SRY后,还发现了许多其他与性别控制和性腺发育相关的基因。由于海水养殖动物的性别控制技术在遗传育种和生产中十分重要,因此利用现代分子生物技术研究性别控制的基因成为热点。本文综述了鱼类、锯缘青蟹、海龟和海胆等水产养殖动物性别控制基因的研究进展。     

己烯雌酚对成年雄性金色中仓鼠的生殖毒性与氧化损伤的关系

为研究环境雌激素己烯雌酚(DES)的生殖毒性与活性氧(ROS)的关系,连续7天给成年金色中仓鼠皮下注射0、0.01、0.1、1mg/kgBWDES,称量睾丸重量、计算睾丸相对重量,光镜观察睾丸组织结构的变化,分光光度法检测睾丸组织和血浆中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、总抗氧化能力(T-AOC)和丙二醛(MDA)的含量。结果表明:1mg/kgBWDES导致睾丸萎缩、重量下降,曲细精管中生精细胞排列紊乱,管腔内几乎没有成熟精子;随着DES剂量的增加,睾丸组织中SOD、GSH-Px和T-AOC含量显著下降,MDA显著上升。提示DES的生殖毒性与ROS密切相关,DES通过降低抗氧化酶水平,增加ROS含量,干扰生精细胞正常功能,导致细胞死亡,表明氧化损伤可能是环境雌激素生殖毒性的作用机理之一。     

围产期克罗米酚处理改变雄性小鼠性取向

由于体内激素水平的变化,围产期和青春期是决定动物大脑发育的关键和敏感时期,而大脑发育是成年动物性取向行为的生物基础。该研究根据这一假说,对实验动物分别于围产期给予药物处理或于青春期予以阉割,并观察其个体成年后的性取向行为。结果显示,围产期克罗米酚(clomiphene citrate)处理9 d(分娩前3天到生育后6天)和14 d(分娩前7天到生育后7天)组,雄性后代的同性取向和雌性化行为明显增多,而正常生长状态下的21日龄雄性后代经阉割后,其性取向无明显改变。即围产期抑制雌激素,可导致雄性小鼠大脑雌性化,产生同性取向,且围产期雌激素对动物雄性化的影响较青春期更为明显。     

雌激素β受体和疼痛

雌激素因具有广泛的生物学效应,而日益成为研究的热点。目前已经清楚雌激素通过雌激素α受体所发挥经典作用,但雌激素β受体的具体作用及机制尚不明晰。通过对雌激素β受体的研究发现,其在性别分化、学习和记忆、情绪调控、内分泌,以及生殖行为中均具有重要作用。本文就雌激素β受体与疼痛相关的研究进展作一综述。     

动物的性选择

有性生殖为个体之间设置了一个冲突和竞争的环境,因为雌雄个体都希望最大限度地把自己的基因传递给后代。性选择保证了动物的繁殖成功。性选择可以分为性别内选择和性别间选择。性别内选择促使动物格斗器官或其他有利于在格斗中获胜的一些特征得到发展;性别间选择促使用来吸引异性的一些特征得到发展。雌性动物的配偶选择或与所选择的特征协同进化,或可以从选择中得到直接的利益。     

Female infertility--effect of perinatal xenoestrogen exposure on reproductive functions in animals and humans

Environmental chemicals with inherent estrogenic activity are supposed to be responsible for the decrease of quantity and quality of human sperms during the past 40 years. The current hypothesis is that estrogenic agents acting during fetal life may lead to impaired development of the testes and of the male reproductive tract in the human as well as in several wildlife species. However, from clinical and experimental data it is known, that estrogens may also lead to impairment of female reproductive functions. Perinatal application of DDT, octylphenol and benzylbutylphthalate resulted in persistent estrus in rats, in- and subfertility, respectively, and impaired sexual behaviour. Epidemiological and experimental data speak in favour of environmental estrogens to be one cause for the development of polycystic ovaries, being the most important reason for female infertility in the human.     

环境雌激素的生殖毒性的分子机理研究进展

环境激素（environmental endocrines,EEs）是外源性激素,可模拟体内天然激素与机体内的受体以及相应靶点结合,导致内分泌系统以及生殖系统功能紊乱。环境激素所产生的效应十分复杂,因此,进一步明确其毒性机理将为环境激素所致危害的预防和治疗提供理论依据。就环境雌激素的生殖、发育等毒性机理作一综述。     

环境雌激素的微生物代谢

环境雌激素作为一类重要的新型环境污染物,可通过干扰生物体的内分泌系统危害生物体健康。微生物降解是去除环境雌激素与进行环境修复的主要手段。本文归纳整理了目前研究较深入的雌激素降解微生物,类比阐述了其预测的降解通路与降解机制,并对后续环境雌激素降解研究的主要内容与方向进行了展望。     

Hormone als Schadstoffe?

Environmental estrogens Endocrine disrupters are environmental substances which interfere with the hormone system of organisms and thereby induce adverse effects. They exert their biological activity either by disrupting hormone metabolism or by imitating the biological action of the endogenous hormones. In the aquatic environment, an important group of endocrine disrupters is represented by the estrogen‐active compounds, which mimic the female sex hormone, 17β‐estradiol. Both laboratory experiments and field studies on fishes have demonstrated that already very low concentrations of environmental estrogens are able to induce disturbances in the hormone system and hormone‐regulated processes of fishes.     

Sulfonation of environmental estrogens by zebrafish cytosolic sulfotransferases

Environmental estrogen-like chemicals are increasingly recognized as a potential hazardous factor for wildlife as well as humans. We have recently embarked on developing a zebrafish model for investigating the role of sulfonation in the metabolism and adverse functioning of environmental estrogens. Here, we report on a systematic investigation of the sulfonation of representative environmental estrogens (bisphenol A, 4-n-octylphenol, 4-n-nolylphenol, diethylstilbestrol, and 17 alpha-ethynylestradiol) by zebrafish cytosolic sulfotransferases (STs). Of the seven enzymes tested, four zebrafish STs (designated ZF ST #2, ZF ST #3, ZF ST #4, and ZF DHEA ST) exhibited differential sulfonating activities toward the five environmental estrogens tested, with ZF ST #3 being more highly active than the other three. It was further demonstrated that bisphenol A, 4-n-octylphenol, and 4-n-nonylphenol exerted concentration-dependent inhibition of the sulfonation of 17 beta-estradiol, implying a potential role of these environmental estrogens in interfering with the sulfonation, and possibly homeostasis, of endogenous estrogens. Kinetic studies revealed that the mechanism underlying the inhibition by bisphenol A or 4-n-nonylphenol to be of the competitive type.     

Environmental estrogens differentially engage the histone methyltransferase EZH2 to increase risk of uterine tumorigenesis

Environmental exposures during sensitive windows of development can reprogram normal physiologic responses and alter disease susceptibility later in life in a process known as developmental reprogramming. For example, exposure to the xenoestrogen diethylstilbestrol during reproductive tract development can reprogram estrogen-responsive gene expression in the myometrium, resulting in hyperresponsiveness to hormone in the adult uterus and promotion of hormone-dependent uterine leiomyoma. We show here that the environmental estrogens genistein, a soy phytoestrogen, and the plasticizer bisphenol A, differ in their pattern of developmental reprogramming and promotion of tumorigenesis (leiomyomas) in the uterus. Whereas both genistein and bisphenol A induce genomic estrogen receptor (ER) signaling in the developing uterus, only genistein induced phosphoinositide 3-kinase (PI3K)/AKT nongenomic ER signaling to the histone methyltransferase enhancer of zeste homolog 2 (EZH2). As a result, this pregenomic signaling phosphorylates and represses EZH2 and reduces levels of H3K27me3 repressive mark in chromatin. Furthermore, only genistein caused estrogen-responsive genes in the adult myometrium to become hyperresponsive to hormone; estrogen-responsive genes were repressed in bisphenol A-exposed uteri. Importantly, this pattern of EZH2 engagement to decrease versus increase H3K27 methylation correlated with the effect of these xenoestrogens on tumorigenesis. Developmental reprogramming by genistein promoted development of uterine leiomyomas, increasing tumor incidence and multiplicity, whereas bisphenol A did not. These data show that environmental estrogens have distinct nongenomic effects in the developing uterus that determines their ability to engage the epigenetic regulator EZH2, decrease levels of the repressive epigenetic histone H3K27 methyl mark in chromatin during developmental reprogramming, and promote uterine tumorigenesis.     

Exposure with the environmental estrogen bisphenol A disrupts the male reproductive tract in young mice

Environmental estrogens (endocrine disruptive chemicals) have been shown to affect reproduction in wild life and it has been reported that maternal exposure with those chemicals have adverse effects on the male reproductive tract. However, little is known about the potential effects of prepubertal or pubertal exposure with environmental estrogens on the male reproductive tract. Here we examine plasma hormone levels and histology in the testis of mice following either 4- or 8-week oral administration of bisphenol A. Plasma free testosterone levels were dramatically decreased following 8 weeks of bisphenol A treatment compared with control group and morphologically multinucleated giant cells having greater than three nuclei were found in seminiferous tubules in the testis following the 8-week bisphenol A treatment. No differences in plasma corticosterone and luteinizing hormone levels were seen between bisphenol A and control groups. Thus, exposure with bisphenol A around pubertal period may directly disrupt the male reproductive tract. These facts suggest that more detailed studies will warrant the assessment of the risk to the developing human testis from exposure to bisphenol A and other environmental estrogens in prepubertal and pubertal period.     

Histological changes in the uterus of the hens after embryonic exposure to bisphenol A and diethylstilbestrol

Many employed chemicals in industries have estrogenic hormone effects on organisms, and these are called as environmental estrogens. Environmental estrogens have adverse effects on development and function of reproductive organs of the birds. Bisphenol A (BPA) is one of the best known environmental estrogens widely found in plastic products. In this study, we injected BPA and the synthetic estrogen diethylstilbestrol (DES) in ovo and then examined and compared the effects of those on the uteri (shell gland) of the adult hens by histological methods. Five groups have been designed in the current study. Only vehicle substance was given in ovo to the control group and BPA (67 or 134 μg/g egg) and DES (0.02 or 0.2 μg/g egg) were administered in the experimental groups. Tissue specimens were taken from uteri of hens at 21 weeks of age, prior to the laying period. Estrogen receptor alpha (ERα) was immunohistochemically stained. It was observed that the hatching proportion in BPA (67 μg and 134 μg/g) was lesser than the other groups (P?<?0.01). Uterine tubular glandular density and thickness of tunica mucosa were found to have reduced (P?<?0.01) in BPA (134 μg/g) and DES (0.2 μg/g) groups, in comparison with those of the control and the other experimental groups. Uterine gland epithelium revealed positive immunoreaction for ERα. These findings suggested that administration of BPA and DES at high doses affected embryonic development in a negative way, and this adverse effect was seen less in adult period.     

Oestrogènes et reproduction masculine

The role of estrogen on male reproductive function has become clearer in the last decade. During these years the study of the effect of testosterone, estrogen or an aromatase inhibitor in hypogonadal men provided a first evidence of the effects of estrogens in the regulation of gonadotropin secretion. At the same time, the development of a line of transgenic male mice lacking estrogen receptor α, estrogen receptor β or aromatase gene provided further evidence about the role of estrogens not only in the regulation of gonadotropin secretion, but also on the effects of estrogens on testicular function and development. A confirmation of these actions of estrogens came from the observation of naturally occurring mutations of the estrogen receptor and of the aromatase gene in human males. Based on these data it has been demonstrated that estrogens are major regulators of gonadotropin secretion acting both at pituitary and hypotalamic level. The presence in the human reproductive structures of estrogen receptor α, estrogen receptor β and the aromatase enzyme indicates the existence of receptor α, estrogen receptor β or aromatase estrogen actions at this level. Anyway, the precise role of estrogens in testicular development and function and on the regulation of human spermatogenesis has not yet been precisely clarified.     

Estrogens and male reproduction

The role of estrogen on male reproductive function has become clearer in the last decade. During these years the study of the effect of testosterone, estrogen or an aromatase inhibitor in hypogonadal men provided a first evidence of the effects of estrogens in the regulation of gonadotropin secretion. At the same time, the development of a line of transgenic male mice lacking estrogen receptor α, estrogen receptor β or aromatase gene provided further evidence about the role of estrogens not only in the regulation of gonadotropin secretion, but also on the effects of estrogens on testicular function and development. A confirmation of these actions of estrogens came from the observation of naturally occurring mutations of the estrogen receptor and of the aromatase gene in human males. Based on these data it has been demonstrated that estrogens are major regulators of gonadotropin secretion acting both at pituitary and hypotalamic level. The presence in the human reproductive structures of estrogen receptor α, estrogen receptor β and the aromatase enzyme indicates the existence of receptor α, estrogen receptor β or aromatase estrogen actions at this level. Anyway, the precise role of estrogens in testicular development and function and on the regulation of human spermatogenesis has not yet been precisely clarified.