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脂溶性激素对生物的生长、发育、分化、器官的生理活动等方面有重要的影响 ,这类激素能直接穿膜进入胞内 ,通过与胞质或核内的特异受体结合而调节基因的表达。 1 988年 ,Giguere等[1] 发现一类新的核受体 (hu manestrogen receptorrelatedreceptor ,hERR) ,由于发现之初未鉴定到其相应的配体 ,称为孤儿受体。核受体大致可分 4个家族 :类固醇类受体、RXR异二聚类受体、同二聚类孤儿受体和单体类孤儿受体 ,绝大多数孤儿受体属于第三、四类。近年陆续鉴定到一些孤儿受体的配体 ,说明孤儿受… 相似文献
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在哺乳动物中,黄体的主要功能是合成并分泌孕酮,同时还合成适量的雌二醇。孕酮不但是发情周期长短的主要调节因子,而且也为胚胎植入与发育创造合适条件。这些类固醇激素通过特异性核受体对其靶细胞发挥作用,这些受体又属于受体依赖性转录因子家族。其中,孕酮是通过其核受体亚型A或B对靶细胞发挥生理功能,而雌二醇是通过其α或β受体对靶细胞发挥生理功能。另外,这些类固醇激素还可以通过细胞膜上类固醇激素结合蛋白,迅速激活胞内信号通路发挥功能,包括孕酮膜受体组分1和2、孕酮膜受体α、β和γ,以及G蛋白偶联的雌二醇受体。该文通过阐述黄体类固醇激素受体的分子结构、生理功能及其调节机制,旨在进一步理解类固醇激素受体在黄体生理功能调节中的重要作用。 相似文献
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类固醇激素受体 (SR)包括糖皮质激素受体 (GR)、孕激素受体 (PR)、雌激素受体(ER)、雄激素受体 (AR)等 ,其中以前两者的研究较多。SR主要存在于类固醇激素的靶细胞胞质和胞核中 ,当细胞外液中类固醇激素通过细胞膜进入胞质后 ,它能与胞质中SR结合 ,通过胞质和胞核中SR的穿梭 ,从而调节核基因组相关产物的转录、翻译及分泌一些生物活性物质 ,以发挥类固醇激素的作用。SR在细胞内有游离形式和复合物形式 ,而且存在几种不同的复合物形式 ,它们是怎样形成以及形成后如何转运到核内的 ?本文将对此作一综述。1 .SR复合物的组… 相似文献
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核受体辅助因子及其信号转导 总被引:2,自引:0,他引:2
类固醇激素、核受体及其辅助因子在细胞增殖、分化中起重要的作用。核受体与相应的配体结合后同细胞内的辅助激活因子CBP/P300、PCAF、P/CIP和SRC家族等结合形成的复合物能使组蛋白乙酰化促进基因的转录,当缺乏配体时核受体同辅助抑制因子SMRI、mSin3A及HAD1具有很强的结合力使组蛋白去乙酰化抑制基因的转录活性。MAPK、PKA、AP-1、Sap-a、JAK/STAT、JAK信号传导中核受体辅助因子参与信号传导过程影响基础的转录。 相似文献
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为深入研究乳腺癌中孤儿受体ERRα1参与基因表达调控的详细机理,特别是核受体辅激活蛋白在其中的作用,以ERRα1的LBD为诱饵,用酵母双杂交系统筛选人乳腺组织cDNA文库得到了与其有明显相互作用的快速骨骼肌型肌钙蛋白I(TNNI2).应用酵母双杂交技术研究表明,TNNI2与多种核受体存在相互作用,且这种作用依赖于功能性的核受体AF2结构域.在哺乳细胞瞬时共转染实验中,TNNI2显示了对多种核受体反式激活功能的辅助活化作用.研究证明,TNNI2与许多辅激活蛋白类似,以配体依赖(对类固醇激素受体而言)或非依赖(对孤儿受体而言)的方式与核受体功能性AF2结构域相互作用,并增强多种核受体介导的反式作用. 相似文献
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类固醇激素作用的非基因组效应崔肇春(大连医科大学生化教研室,大连116027)关键词类固醇激素非基因组效应六十年代发现了类固醇激素的胞内受体,促进了类固醇激素作用机制的研究。众所周知,类固醇激素作用的途径是它直接进入细胞后,与胞内受体结合成激素-受体... 相似文献
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雌激素受体与神经系统疾病 总被引:2,自引:0,他引:2
雌激素受体是类固醇激素受体超家族成员之一,是一种配体依赖性转录因子,具有广泛的生物学功能。雌激素受体在脑内具有广泛的分布,且与一些神经系统疾病的发生发展相关。就雌激素受体在脑内的分布及其与神经系统疾病的关系进行论述。 相似文献
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Integration of the extranuclear and nuclear actions of estrogen 总被引:21,自引:0,他引:21
Levin ER 《Molecular endocrinology (Baltimore, Md.)》2005,19(8):1951-1959
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Adrien Grimont 《FEBS letters》2009,583(10):1644-262
Renal functions are regulated by steroid sex hormones, but the exhaustive identification of their receptors along the nephron is still lacking. Here, we have localized all known nuclear or membrane-bound sex hormone receptors and some of their activators along the nephron of male and female mice. Almost all receptors are present in male and female kidney, some of them having very restricted localization. Only one gene tested among 11 (ARA54) exhibits a gender difference in the level of its expression. This first “renal map” of sex steroid receptor expression may serve as a pre-requisite for investigating the role of these hormones on kidney functions. 相似文献
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Estrogen receptors and androgen receptors in the mammalian liver 总被引:2,自引:0,他引:2
An estrogen receptor and an androgen receptor are present in the mammalian liver. In the liver of the rat, the estrogen receptor concentration increases markedly at puberty and this change correlates with enhanced estrogen stimulation of plasma renin substrate synthesis. High doses of estrogen are required for nuclear binding in liver when compared to doses for the uterus. The high dose requirement appears to be predominantly due to extensive metabolism in the hepatocyte of the estrogen to inactive derivatives. Furthermore, estradiol is much weaker than ethinyl estradiol for promoting nuclear binding in the liver. This is due to extremely rapid and extensive metabolism of estradiol. In human liver the concentration of estrogen receptor is low. An androgen receptor is present in high concentration in rabbit liver and is located predominantly in the nucleus after androgen administration. High concentrations of a putative androgen receptor are also present in human liver cytosol. Preliminary studies indicate that synthetic progestins can attach to the human liver androgen receptor. To date, a progesterone receptor has not been found in the mammalian liver. Thus, it appears that extensive steroid metabolism in liver preferentially diminishes sex steroid interaction with liver receptors and that androgen receptors may mediate progestin effects in liver. These observations provide a scientific basis for improved safety of oral contraceptives. Lowering the estrogen and progestin doses in oral contraceptives will decrease the major side-effects, which are liver mediated, and still maintain the desired effects at the hypothalamic-pituitary axis and uterus. Furthermore, it is likely that by selecting which estrogen, progestin or androgen is administered as well as by utilizing a parenteral route of administration that sex steroid effects on the liver could be minimized. 相似文献
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Steroid hormone receptor localization in the nuclear matrix: interaction with acceptor sites 总被引:4,自引:0,他引:4
E R Barrack 《Journal of steroid biochemistry》1987,27(1-3):115-121
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From the structure of steroid receptors to their assessment by immunocytochemistry in target cells 总被引:1,自引:0,他引:1
Immunohistochemical studies with antibodies to steroid hormone receptors provide new insight in the mechanism of action of steroid hormones. Immunologically reactive estrogen and progesterone receptors are found exclusively in cell nuclei of target cells even in the absence of the hormonal ligand. A hormonal treatment inducing receptor transformation and "translocation" to the nucleus does not modify the intracellular distribution of the receptor. This result is in contradiction with most biochemical studies which show a displacement of receptor from the cytosolic fraction to the nuclear fraction after hormone-receptor complex formation. We propose that different affinity levels of the non-transformed and hormone-complexed receptor molecules for nuclear structure produce unequal losses of nuclear receptor during homogenization. A lesser loss appears as an increase in nuclear binding sites or immunologically reactive receptor. The glucocorticosteroid receptor differs from the others in that it shows an increase of nuclear immunoreactive receptor after hormone administration. This result was accepted as evidence for a nuclear translocation in the sense initially proposed for all steroid hormones. Alternatively, one may propose another explanation based on the same experimental artefact as invoked for the estrogen and progesterone cytosol receptors. A higher affinity of the hormone-complexed receptor entails a lesser loss from the nucleus during tissue processing, and consequently an apparent increase in nuclear staining. Such a possibility is currently tested in parallel with the progesterone receptor. 相似文献
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The expression pattern of MUC1 glycoforms and other biomarkers of endometrial receptivity in fertile and infertile women 总被引:4,自引:0,他引:4
Horne AW Lalani EN Margara RA Ryder TA Mobberley MA White JO 《Molecular reproduction and development》2005,72(2):216-229
Changes in the surface epithelium of the endometrium, characterized in part by alterations in cell-surface molecules, sex steroid receptors and the appearance of pinopodes, coincide with the window of endometrial receptivity in the menstrual cycle. This study was performed to evaluate the usefulness of hematoxylin and eosin staining, scanning and transmission microscopy, and MUC1 glycoform, sex steroid receptor, and interleukin receptor (type 1) expression as biomarkers of endometrial receptivity using carefully characterized clinical fertile and infertile groups of women. Using a combination of immunohistochemistry and scanning electron microscopy (SEM) called scanning immunoelectron microscopy (SIM), we confirmed that MUC1 mucin was not associated with the endometrial pinopodes, which have been linked with embryo adhesion. We also showed that failure of embryo implantation was associated with an abnormal endometrial expression of MUC1 mucin, and retention of nuclear progesterone receptor (PR) particularly in epithelial cells. Hematoxylin and eosin staining, transmission electron microscopy (TEM), SEM in isolation and immunohistochemistry for interleukin receptor were not shown to be useful markers. Progesterone-dependent regulation of MUC1 appears to be an important factor in determining endometrial receptivity. 相似文献