白藜芦醇生物学活性研究进展

白藜芦醇是一种植物抗毒素,主要存在于虎杖、葡萄及花生等有限的植物中,它具有对人体有益的生物学活性,如具有拮抗肿瘤作用、心血管保护作用、抗炎作用、抗病毒作用、神经保护作用、植物雌激素作用和对骨钙的影响等。     

雌激素在中枢神经系统中的作用

雌激素对中枢神经系统神经元有多种作用（包括电生理、神经营养和代谢等的作用）。近年来,随着对雌激素作用基因组机制和非基因组机制的研究,人们逐渐加深了其在神经功能方面作用 的认识。目前发现,雌激素在调节下丘脑ＧnRH神经元功能活动、诱导和维持海马树状棘突,以及保护神经元等诸多方面都发挥着重要作用。流行病学提示,雌激素可以预防绝经妇女患早老性痴呆病（Alzheimer‘sDisease,AD)对神经功能有保护作用,由此可见,雌激素除调节生殖功能活动外,对中枢神经系统还有着更为广泛的作用。     

植物雌激素的作用

植物雌激素是一类具有雌激素活性的化合物,自然界来源广泛。该文介绍植物雌激素对肿瘤、心血管系统、神经系统和生殖系统等的作用。植物雌激素具有广阔的临床应用前景,但还需进一步研究,了解其副作用及作用机制。     

植物雌激素与乳腺癌发病发展的研究进展

总结植物雌激素(phytoestrogen,PE)在乳腺癌发病、发展过程中的研究进展。应用Medline、Embase、CNKI及VIP数据库检索"植物雌激素、乳腺癌"相关基础临床试验流行病学调查。PE作为非甾体结构的雌激素类似物,能够与雌激素受体结合产生作用。目前研究主要集中于PE通过雌激素受体对乳腺癌细胞的增殖、凋亡、自噬、周期的影响和信号传导通路的研究,体外实验PE有抑制乳腺癌细胞增殖、促进凋亡、自噬的作用,但是对转移的作用不明确,可通过PI3K/AKT和ROS/p38MAPK途径诱导凋亡,PE与ER结合或调整ERα/ERβ达到抑制乳腺癌细胞的作用,流行病学调查未发现PE对人体有害,鲜有临床报道。因此,本文对PE对乳腺癌的研究进展进行总结分析,旨在为乳腺肿瘤患者治疗提供新方向。植物雌激素有希望成为乳腺肿瘤患者治疗的新方向。     

高等植物中的萜类化合物及其在生态系统中的作用

植物通过次级代谢途径产生的物质称为次生代谢产物(ｓｅｃｏｎｄａｒｙｐｒｏｄｕｃｅ)。作为代谢的末端产物 ,它们通过降解或合成产生 ,不再对代谢过程起作用。这些产物是在植物体内合成的 ,但对维持植物的基本生命活动尚无确定作用。既然这些次生代谢物质对植物的基本生命活动没有明显的作用 ,为什么植物要合成它们呢 ?到目前为止 ,已经初步明确植物次生代谢物质的主要功能表现为两个方面。首先 ,它们具有重要的生态学意义自身防御和繁衍后代。为了生存 ,植物合成和利用这些次生代谢物质既可以阻止其它生物的侵害 ,又可以抑制与其竞争生存…     

植物性雌激素心血管效应的研究进展

植物性雌激素（phytoestrogen)是一类天然存在于植物中,与雌激素结构近似的生物活性物质,本文介绍了它的来源和种类,阐述了其对心脏功能,心肌电生理和血管的效应。植物性雌激素具有舒张冠脉,抗动脉粥样硬化等心血管保护作用,为防治心血管疾病的研究开辟了新的思路。     

雌激素的神经保护作用

雌激素是一种性激素 ,它的主要生理作用是促进女性生殖器官的发育与成熟 ,刺激女性副性征出现 ,并影响代谢功能。然而 ,雌激素的作用并不仅局限于此 ,它在大脑的正常发育、分化中也起着重要作用。目前发现 ,雌激素除了能通过调节下丘脑ＧｎＲＨ神经元的活动影响生殖外 ,对大脑其它神经元还有着电生理、神经营养和代谢等多方面作用 ,而其中备受关注的是它对中枢神经元的保护作用。临床证实 ,雌激素替代治疗 (ＥＲＴ)可以明显改善绝经后妇女的认知功能 ,对于老年性痴呆病 (Ａｌｚｈｅｉｍｅｒ’ｓｄｉｓｅａｓｅ ,ＡＤ)、缺血性脑损伤以及神经…     

雌激素对MAPK信号转导通路的作用机制

雌激素可以通过基因组作用和非基因组作用对细胞功能起调节作用。本文主要综述了其非基因组作用,即通过膜受体激活细胞内MAPK(ERK、p38、JNK)信号传导通路的过程。雌激素对ERK主要起促进作用,引起细胞增殖、分化以及血管扩张等生物学效应;对p38也起促进作用,而在不同的细胞中对JNK的作用不同,进而调节细胞凋亡、癌症发生等生命现象。     

雌激素及其受体在内耳发育和功能上的作用

雌激素在生殖系统、认知记忆系统、骨骼和神经的发育及其功能维持等多种生理功能中扮演了重要的作用。近年来,在内耳发育及其功能研究过程中,许多学者发现在听力和平衡系统功能上的性别差异可能归根因于不同性别的雌激素水平差异。这些研究表明,雌激素及其受体在内耳发育、听力和平衡系统功能维持上也具有重要作用。该文用一个新的视角聚焦于雌激素及其受体在内耳发育和功能上的研究进展。该综述能为进一步研究雌激素在听力和平衡系统中的作用机制及相关疾病的临床治疗提供参考。     

高寒草甸对刈割、施肥和浇水发生响应的最优植物性状集和功能型

基于植物性状和功能型的特征变化对于研究植被动态和生态系统功能变化具有重要意义。通过在高寒矮嵩草(Kobresia humilis)草甸为期5年(2007-2011年)的刈割(不刈割、留茬3 cm、留茬1 cm)、施肥(施肥、不施肥)和浇水(浇水、不浇水)控制实验, 采用递归算法(recursive algorithm)和多元回归分析筛选对模拟放牧发生响应的最优植物性状集和响应功能型, 以及影响群落生产力变化的作用功能型。研究结果显示: (1)在不施肥不浇水、仅施肥、仅浇水和既施肥又浇水4种条件下的最优植物性状集不同, 它们分别是叶缘形状-株高-叶干质量-比叶面积、生活周期-株高-叶干质量-比叶面积、生活周期-叶片叶绿素含量-叶表面结构-株高-叶干质量-比叶面积和繁殖结构-叶缘-株高。其中, 株高、叶干质量和比叶面积是对刈割和土壤资源变化更为敏感的植物性状。(2)在这4种处理条件下, 共获得14个最优响应功能型和4个作用功能型。作用功能型对群落生产力变异的解释能力在50.3%-86.4%之间。(3)最优响应功能型和作用功能型分别占功能型总数的70%和20%。作用功能型占最优响应功能型的28.5%, 两者间仅存在部分重叠。上述结果说明, 植物功能性状和功能型变化能够准确地反映植被的放牧响应和生态系统功能变化, 但是不同资源条件下群落的最优响应性状集和功能型不同。作用功能型是同时反映植被放牧响应和生态系统功能变化的最优功能型。     

The human estrogen receptor can regulate exogenous but not endogenous vitellogenin gene promoters in a Xenopus cell line.

Transfection of a human estrogen receptor cDNA expression vector (HEO) into cultured Xenopus kidney cells confers estrogen responsiveness to the recipient cells as demonstrated by the hormone dependent expression of co-transfected Xenopus vitellogenin-CAT chimeric genes. The estrogen stimulation of these vit-CAT genes is dependent upon the presence of the vitellogenin estrogen responsive element (ERE) in their 5' flanking region. Thus, functional human estrogen receptor (hER) can be synthesized in heterologous lower vertebrate cells and can act as a trans-acting regulatory factor that is necessary, together with estradiol, for the induction of the vit-CAT constructs in these cells. In addition, vitellogenin minigenes co-transfected with the HEO expression vector also respond to hormonal stimulation. Their induction is not higher than that of the vit-CAT chimeric genes. It suggests that in the Xenopus kidney cell line B 3.2, the structural parts of the vitellogenin minigenes do not play a role in the induction process. Furthermore, no stabilizing effect of estrogen on vitellogenin mRNA is observed in these cells. In contrast to the transfected genes, the endogenous chromosomal vitellogenin genes remain silent, demonstrating that in spite of the presence of the hER and the hormone, the conditions necessary for their activation are not fulfilled.     

ICAM-1 expression in vaginal cells as a potential biomarker for inflammatory response

This study aimed to elucidate the mechanisms that may lead to an efficient strategy to induce a suitable host response of the vaginal mucosa upon exposure to intravaginally delivered exogenous compounds. It was hypothesized that the upregulation of intercellular adhesion molecule (ICAM)-1 gene expression may reflect the inflammatory response evoked by exogenous compounds. Major emphasis was placed on ethylenediamine tetraacetic acid (EDTA) which was added as a synergistic agent to conventional spermicidal agents or anti-HIV drugs. The levels of ICAM-1 mRNA were examined as a surrogate marker for inflammatory response in human vaginal epithelial cells upon exposure to EDTA or interleukin (IL)-1β (i.e. positive control, 25 mM). The effects of estrogen on EDTA-induced ICAM-1 expression were also evaluated for the estrogen involvement in the inflammatory process of the vaginal mucosa. ICAM-1 expression in human vaginal cells (VK2/E6E7 cells) increased as EDTA concentration added to human vaginal cell lines increased. The effects of estrogen on EDTA-induced ICAM-1 expression in human vaginal epithelial cells were estrogen-concentration dependent; estrogen at lower concentrations (～1–10 nM) did not affect ICAM-1 expression, whereas estrogen at higher concentrations (～100 nM–1 µM) attenuated ICAM-1 expression. The influence of estrogen in ICAM-1 expression suggests the beneficial effects of estrogen on the regulation of vaginal homeostasis. Identification and quantification of specific surrogate markers for the inflammatory response evoked by exogenous compounds and their regulation by estrogen will lead to an efficient strategy against sexually transmitted diseases including AIDS.     

ICAM-1 expression in vaginal cells as a potential biomarker for inflammatory response

This study aimed to elucidate the mechanisms that may lead to an efficient strategy to induce a suitable host response of the vaginal mucosa upon exposure to intravaginally delivered exogenous compounds. It was hypothesized that the upregulation of intercellular adhesion molecule (ICAM)-1 gene expression may reflect the inflammatory response evoked by exogenous compounds. Major emphasis was placed on ethylenediamine tetraacetic acid (EDTA) which was added as a synergistic agent to conventional spermicidal agents or anti-HIV drugs. The levels of ICAM-1 mRNA were examined as a surrogate marker for inflammatory response in human vaginal epithelial cells upon exposure to EDTA or interleukin (IL)-1β (i.e. positive control, 25 mM). The effects of estrogen on EDTA-induced ICAM-1 expression were also evaluated for the estrogen involvement in the inflammatory process of the vaginal mucosa. ICAM-1 expression in human vaginal cells (VK2/E6E7 cells) increased as EDTA concentration added to human vaginal cell lines increased. The effects of estrogen on EDTA-induced ICAM-1 expression in human vaginal epithelial cells were estrogen-concentration dependent; estrogen at lower concentrations (∼1-10 nM) did not affect ICAM-1 expression, whereas estrogen at higher concentrations (∼100 nM-1 µM) attenuated ICAM-1 expression. The influence of estrogen in ICAM-1 expression suggests the beneficial effects of estrogen on the regulation of vaginal homeostasis. Identification and quantification of specific surrogate markers for the inflammatory response evoked by exogenous compounds and their regulation by estrogen will lead to an efficient strategy against sexually transmitted diseases including AIDS.     

Intracellular aromatase and its relevance to the pharmacological efficacy of aromatase inhibitors

An important feature of the pharmacological profile of aromatase inhibitors is the ability of the various inhibitors to inhibit intracellular aromatase. It is now well documented that a large proportion of breast tumors express their own aromatase. This intratumoral aromatase produces estrogen in situ and therefore may contribute significantly to the amount of estrogen to which the cell is exposed. Thus it is not only important that aromatase inhibitors potently inhibit the peripheral production of estrogen and eliminate the external supply of estrogen to the tumor cell, but that they in addition potently inhibit intratumoral aromatase and prevent the tumor cell from making its own estrogen within the cell. To study the inhibition of intracellular aromatase we have compared the aromatase-inhibiting potency of the non-steroidal aromatase inhibitors, letrozole, anastrozole and fadrozole in a variety of model cellular endocrine and tumor systems which contain aromatase. We have used hamsters ovarian tissue fragments, adipose tissue fibroblasts from normal human breast, the MCF-7Ca human breast cancer cell line transfected with the human aromatase gene and the JEG-3 human choriocarcinoma cell line. Although letrozole and anastrozole are approximately equipotent in a cell-free aromatase system (human placental microsomes), letrozole is consistently 10–30 times more potent than anastrozole in inhibiting intracellular aromatase in intact rodent cells, normal human adipose fibroblasts and human cancer cell lines. Whether these differences between letrozole and anastrozole are seen in the clinical setting will have to await the results of clinical trials which are currently in progress.     

Construction of cell lines that express high levels of the human estrogen receptor and are killed by estrogens

To prepare large amounts of the human estrogen receptor (ER) for biochemical and biophysical studies we have employed the cloned ER sequences to construct Chinese hamster ovary (CHO) cell line derivatives that overexpress the receptor. We have employed an efficient expression vector (SV40 enhancer, human metallothionein IIA promoter) and a new system of gene amplification based on the human metallothionein IIA gene and stepwise selection in cadmium. Cells from the initial transfected pools, before gene amplification, had as much or more ER than human MCF7 cells and responded to the subsequent stepwise cadmium selection and amplification with increases in ER levels to about 2 million receptors/cell. Cell lines isolated from these pools are stable for human ER expression and display up to 6 million receptors/cell, or about 0.4% of the total cell protein. The CHO receptor activates a transfected reporter gene in responses to estrogen, is down-regulated in response to estrogens, displays the same electrophoretic mobility as the MCF7 receptor, and is free of degradation as initially extracted. CHO cells displaying 3 million or more human ER/cell (but not cells with lower levels) flatten and stop growing within the first 24 h after exposure to physiological estrogen concentrations. After several days in estrogen the majority of the cells lyse. The antiestrogen 4-hydroxytamoxifen also causes cell death, but another antiestrogen, ICI 164,384, is without toxic effect. The basis for these phenomena are unknown, but mutants isolated for survival of estrogen treatment have lost receptor expression, thereby confirming the role of receptor in cell death.     

Conserved estrogen binding and signaling functions of the G protein-coupled estrogen receptor 1 (GPER) in mammals and fish

Recent studies by several research groups have shown that G protein estrogen receptor-1 (GPER) formerly known as GPR30, mediates 17β-estradiol (E2) activation of signal transduction pathways in a variety of human cancer cells and displays E2 binding typical of a membrane estrogen receptor. However, the importance of GPER as an estrogen receptor has been questioned by Otto and co-workers. Some of the pitfalls in investigating the functions of recombinant steroid membrane receptors that may explain the negative results of these investigators are discussed. The characteristics of GPER have also been investigated in a teleost fish, Atlantic croaker, where it has been shown to mediate E2 inhibition of oocyte maturation. Investigations on newly discovered homologous proteins from distantly related vertebrate groups are valuable for determining their fundamental, evolutionarily conserved functions. Therefore, the functions of croaker and human GPERs were compared. The comparisons show that croaker and human GPER have very similar estrogen binding characteristics, typical of estrogen membrane receptors, and activate the same estrogen signaling pathways via stimulatory G proteins (Gs) resulting in increased cAMP production. These results suggest that the estrogen binding and estrogen signaling functions of GPER arose early in vertebrate evolution, prior to the divergence of the teleosts from the tetrapods, more than 200 million years ago. The finding that estrogen membrane signaling through GPER has been conserved for such a long period in two distantly related vertebrate groups, mammals and fish, suggests that this is a fundamental function of GPER in vertebrates, and likely its major physiological role.     

Urinary estrogen excretion during pregnancy in the gorilla (Gorilla gorilla), orangutan (Pongo pygmaeus) and the human (Homo sapiens)

Urinary estrogen components were separated, identified and quantified throughout the pregnancy of the gorilla (Gorilla gorilla) and orangutan (Pongo pygmaeus) and compared to estrogen levels in normal human pregnancies. Fetal and neonatal adrenals from each species were also compared in terms of weight and relative amounts of fetal zone. The results demonstrate that gorillas and chimpanzees excrete 4- to 5-fold less estrogen during pregnancy than the human and orangutan which are similar to each other. The lower estrogen excretion appears to be related to a smaller fetal adrenal in both the gorilla and chimpanzee which reveal both a reduced adrenal weight and increased definitive to fetal zone ratio when compared to either the human or orangutan.     

Autocrine and paracrine growth regulation of human breast cancer

Previous work from our laboratory has demonstrated that human breast cancer (BC) cells in culture can be stimulated by physiologic concentrations of estrogen. In an effort to further understand this process, we have examined the biochemical and biological properties of proteins secreted by human BC cells in vitro. We have developed a defined medium system which simultaneously allows the collection of factors secreted by the BC cells, facilitates their purification and allows for an unequivocal assay of their effect on other BC cells. By both biochemical and radioimmunoassay procedures, MCF-7 cells secrete large quantities of IGF-I-like activity. The cells contain receptors for IGF-I and are stimulated by physiologic concentrations of IGF-I. Multiple additional peaks of growth stimulatory activity can be obtained by partial purification of conditioned media from human BC cells by sequential dialysis, acid extraction and Biogel P60 chromatography. These peaks are induced up to 200-fold by physiologic concentrations of estrogen. Several of these peaks cross-react in a radioreceptor assay with EGF and are thus candidates for transforming growth factors. Monoclonal antibodies (MCA) have been prepared which react with secreted proteins from the MCF-7 cells. One of these MCAs binds to material from MCF-7 and ZR-75-1 hormone-dependent BC cells only when these two lines are treated with estrogen but reacts with conditioned medium from several other hormone-independent cell lines in the absence of estrogen stimulation. This MCA is currently undergoing further characterization and evaluation of its biological potency. We conclude that with estrogen stimulation, hormone-dependent human BC cells secrete peptides which when partially purified can replace estrogen as a mitogen. Their role as autocrine or paracrine growth factors and their effects on surrounding nonneoplastic stroma may suggest a means of interfering with tumor proliferation.     

Immunoreactive EGF in human benign prostatic hyperplasia: relationships with androgen and estrogen receptors

Benign prostatic hyperplasia (BPH) is a sex steroid dependent disease. Estrogens and androgens can modulate in different mammalian tissues epidermal growth factor (EGF) production and/or secretion. In order to clarify the relationships between estrogen and androgen receptor concentrations and those of immunoreactive EGF (irEGF), we have evaluated these parameters in 14 human BPH samples, by means of a dextran-coated charcoal method and radioimmunoassay, respectively. Cytosolic steroid receptors did not seem to correlate with irEGF. A linear significative relationship was evident between nuclear androgen receptor (ARn) levels and endogenous irEGF but not between nuclear estrogen receptors and irEGF: in ARn negative BPH samples, irEGF levels were lower than in ARn positive ones. Therefore, it is possible that androgens act at prostatic tissue level, through their own receptors, by modulating EGF production and/or secretion.