共查询到19条相似文献,搜索用时 93 毫秒
1.
孕酮调节途径在着床过程中的作用 总被引:2,自引:0,他引:2
孕酮对于哺乳动物排卵、受精、着床、蜕膜化及妊娠维持均起到重要作用.孕酮主要通过孕酮受体(PR)起作用,PR基因敲除的小鼠表现为多种生殖障碍.此外,PR作用的发挥还需要类固醇受体辅助激活因子(SRC)和FK506结合蛋白4(Fkbp52)等辅助因子的参与.目前采用高通量基因芯片技术,筛选出许多直接或间接受孕酮调节的基因,其中同源盒基因、免疫反应基因-1、Indian hedgehog、12 / 15脂肪氧合酶、钙离子结合蛋白等在胚泡着床过程中起重要作用.本文就孕酮调节途径在胚泡着床研究方面的进展作一简要综述. 相似文献
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本文观察了外源性阿片肽对大鼠离体黄体细胞孕酮生成的影响,结果表明:β-内啡肽以剂量-反应依赖方式促进黄体细胞孕酮生成,有效浓度范围是10~(-8)-10~(-6) mol/L;强啡肽仅在浓度为10~(-6)mol/L时才显示刺激孕酮生成的作用;而甲硫-脑啡肽无明显作用。μ-阿片受体激动剂DAGO和乙基吗啡也能明显促进孕酮的生成。纳洛酮可完全阻断β-内啡肽,DAGO和乙基吗啡的作用。由于大鼠血液中β-内啡肽含量较低,而卵巢局部具有较高浓度的β-内啡肽。因此,我们认为,β-内啡肽可能在卵巢局部参与黄体细胞孕酮生成的调节,是卵巢内促黄体因子之一,这种作用可能是由μ-型阿片受体介导的。 相似文献
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β-防御素(β-defensin)在雌性动物生殖道广泛存在,起免疫防御作用.为了研究孕酮与雌性生殖道β-防御素mRNA表达的关系,本实验建立绵羊(Ovis aries)输卵管上皮细胞培养体系,添加不同浓度孕酮(10~(-6),10~(-7),10~(-8),10~(-9)和10~(-10) mol/L)和孕酮拮抗剂米非司酮后提取细胞总RNA,利用实时定量PCR测定β-防御素mRNA的相对表达量.结果显示,一定浓度的孕酮(10~(-6),10~(-7),10~(-8)和10~(-9) mol/L)对培养的输卵管上皮细胞β-defensin mRNA的表达有促进作用,且不同浓度的孕酮对β-defensin mRNA的表达的影响程度不同.米非司酮极显著抑制了孕酮诱导的β-defemin mRNA的表达.结果表明,孕酮通过与孕酮受体结合促进β-defensin mRNA的表达,推断雌性生理周期下孕酮可能通过作用于β-defensin等影响自身免疫. 相似文献
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建立蒙古绵羊输卵管上皮细胞培养体系作为体外实验模型,分别添加10-6、10-7、10-8、10-9和10-10 mol/L孕酮,运用实时荧光定量PCR方法测定孕酮对上皮细胞内β-防御素相对表达量的影响。结果显示,与对照组比较,10-6和10-7 mol/L孕酮组β-防御素相对表达量显著升高(P<0.05);10-8和10-9 mol/L孕酮组极显著升高(P<0.01);而10-10 mol/L孕酮组未见显著性差异。孕酮添加组间比较显示,10-8和10-9 mol/L孕酮组极显著高于10-10 mol/L组(P<0.01),其它孕酮添加组间未见显著性差异。分析认为,一定浓度的孕酮(10-9-10-6 mol/L)对培养的输卵管上皮细胞β-防御素的表达有促进作用。且不同浓度的孕酮对β-防御素表达的影响程度不同。因而推断,雌性生理周期下,雌性生殖道β-防御素的表达与孕激素相关。 相似文献
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目的观察孕酮膜受体(membrane progestin receptors,m PRs)在小鼠子宫、输卵管和卵巢的分布及其周期性变化。方法用实时定量PCR、免疫组织化学分别检测动情期和动情间期小鼠生殖系统m PRs的m RNA及蛋白表达。结果在子宫内,m PRα、β免疫阳性反应分布于内膜上皮、腺体上皮、内膜基质和血管内皮,而m PRγ弱免疫阳性反应见于腺体上皮和血管内皮;在卵巢中,m PRα、β免疫阳性反应见于卵巢间质、卵母细胞和颗粒细胞,m PRγ而未见明显免疫阳性反应;在输卵管中,3种蛋白均未见明显免疫阳性反应。实时定量PCR显示3种m RNA在卵巢、输卵管和子宫均表达,m PRβ的m RNA表达水平最高;动情期和动情间期3种m RNA在卵巢、输卵管和子宫中均有表达,而表达水平无显著性差异。结论 m PRα、β在卵巢和子宫中表达稳定,提示小鼠生殖系统中,孕酮的非基因效应可能更多依赖m PRα、m PRβ的介导,尤其是m PRβ。 相似文献
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用鸡的颗粒细胞(granulosa cell,G·C·)进行极低密度脂蛋白(VLDL)对于孕酮合成的研究。按序列超速离心法分离鸡血清脂蛋白。用放射免疫法测定孕酮的量。实验分组:G·C·加绵羊促黄体生成素(OLH),其浓度范围为1—50 ng/ml,此为OLH组;G·C·加VLDL(最终浓度400μg/ml)再加OLH,此为VLDL组;G·C未加VLDL和OLH则为对照组。实验结果:(1).OLH组能促进G·C·孕酮的合成而且孕酮的生成量随着OLH量的增加而增加。(2)VLDL组孕酮生成量较OLH组显著增高,两者之间有显著性差异(P<0.001)。(3)用3次实验结果合并计算VLDL组和OLH组的平均数相当于对照组平均数的百分数,发现VLDL组明显高于OLH组。实验结果说明VLDL是携带胆固醇的脂蛋白,从而在OLH作用下,使颗粒细胞合成孕酮的量增多。 相似文献
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用免疫细胞化学LSAB法,兔抗人孕酮受体抗体(适用于小鼠)显示小鼠卵巢、输卵管、子宫和阴道中的孕酮受体。结果显示:未注射RU486的动物的子宫与阴道内孕酮受体丰富,输卵管中含量较少,卵巢中未见阳性反应物质。RU486注射4天后,子宫与阴道中孕酮受体明显减少;注射后7天,输卵管、子宫和阴道都为阴性反应。该结果显示了孕酮受体在雌性小鼠生殖系统内的分布特点,提示RU486封闭孕酮受体的最佳时间为用药后第7天。 相似文献
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c-fos、c-myb和c-erbB-2与大鼠卵巢颗粒细胞生孕酮调控关系的研究 总被引:2,自引:1,他引:1
目的和方法:用离体细胞体外孵育法,观察反义c-fos、c-myb和c-erbB-2 寡脱氧核苷酸(c-fos ODN、c-myb ODN和c-erbB-2 ODN)对hCG诱导大鼠颗粒细胞孕酮产生的影响,同时观察内皮素-1、γ-氨基丁酸和钙离子通道阻断剂维拉帕米对颗粒细胞中c -fos、c-myb和c-erbB-2蛋白的影响.结果:反义c-fos、c-myb和c-erbB -2 ODN均明显抑制hCG诱导颗粒细胞孕酮的产生,并伴有各自癌基因蛋白染色阳性的颗粒细胞百分率下降;而无义tat ODN没有相应的作用.2×10-7mol/L内皮素-1和5×10 -6mol/L γ-氨基丁酸能显著抑制hCG诱导颗粒细胞孕酮的产生,同时使c-fos、c-my b和c-erbB-2蛋白染色阳性的颗粒细胞百分率下降;而1×10-6mol/L维拉帕米对hCG 诱导颗粒细胞孕酮的产生和c-fos、c-myb和c-erbB-2蛋白染色阳性的颗粒细胞百分率均无明显影响.结论:c-fos、c-myb和c-erbB-2与hCG诱导颗粒细胞孕酮的产生密切相关;内皮素-1、γ-氢基丁酸能通过调节这些癌基因在颗粒细胞中的表达而影响hCG诱导颗粒细胞孕酮的产生;而Ca2+无相应的作用. 相似文献
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A novel, high-affinity, fluorescent progesterone receptor antagonist. Synthesis and in vitro studies
Hödl C Strauss WS Sailer R Seger C Steiner R Haslinger E Schramm HW 《Bioconjugate chemistry》2004,15(2):359-365
The present paper describes the chemical synthesis and in vitro characterization of a novel, high-affinity, fluorescent progesterone receptor (PR) antagonist. The three-step synthesis was carried out starting from mifepristone. After demethylation with calcium oxide, the methylamino group was alkylated with 6-bromohexanol, and the resulting compound was reacted with fluorescein 5-isothiocyanate, yielding the fluorescein-mifepristone conjugate. Interaction of the conjugate as well as of its precursors with PR was determined in cell culture (alkaline phosphatase assay and transactivation assay). Antiprogestagenic activity of the intermediates were comparable to that of the parent compound. Even after attachment of the bulky fluorescein moiety, considerable antiprogestagenic activity was maintained. Microscopic studies revealed that fluorescence of the conjugate was almost confined to the nuclei of steroid hormone receptor-positive cells, whereas the nuclei of steroid hormone receptor-negative cells remained unstained. To our knowledge, this is the first report on a fluorescent ligand for PR suitable for studies in living cells. It is proposed that the present fluorescent PR antagonist might serve as a lead compound for the development of contrast agents for PR imaging, e.g., by near-infrared optical imaging. 相似文献
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马桑内酯激活的星形胶质细胞条件培养液对正常大鼠脑内孕激素及其受体的影响 总被引:2,自引:1,他引:1
目的探讨星形胶质细胞对大鼠脑内孕激素及其受体的影响以及在癫痫发病中的作用。方法将马桑内酯(Coriaria lactone,CL)激活的星形胶质细胞条件培养液(Astrocytic conditioned medium,ACM)注射入正常SD大鼠侧脑室后,观察大鼠的行为变化;运用免疫组织化学方法观察大脑皮质及海马中孕激素受体(PR)表达的变化;运用放射免疫分析方法,观察脑组织匀浆及脑脊液内孕酮含量的变化。结果ACM组大鼠在注射ACM后30min出现癫痫行为,2h恢复正常;免疫组织化学显示:ACM作用后2h,PR免疫反应阳性神经元数和平均光密度值明显降低,4h达最低(P<0.05),12h恢复正常水平;放射免疫分析方法显示ACM组大鼠在侧脑室注射ACM后2h,脑脊液中孕酮含量明显升高;而海马组织和大脑皮质中孕酮含量则在注药后4h明显降低,与对照组比较均有显著差异(P<0.05)。结论以上实验结果提示马桑内酯激活的星形胶质细胞条件培养液可通过降低大鼠脑内孕激素及其受体的表达参与癫痫的反复发作。 相似文献
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《Bioorganic & medicinal chemistry》2016,24(21):5602-5610
Progesterone is involved in multiple physiological processes, including female reproduction, via binding to the progesterone receptor (PR). We have developed 6-arylcoumarins such as 5 and 6 as non-steroidal PR antagonists with receptor-binding-dependent fluorescence. In this study, we investigated the structure–activity relationships and fluorescence properties of coumarin derivatives bearing a heterocyclic aromatic moiety. Among these derivatives, 7c (IC50: 34 nM) and 10b (IC50: 24 nM) showed more potent PR-antagonistic activity than lead compounds 5 (IC50: 500 nM) and 6 (IC50: 65 nM) in alkaline phosphatase (AP) assay. Compound 9b showed solvent-dependent fluorescence intensity, exhibiting strong fluorescence in the presence of PR LBD only in buffer solution. On the other hand, 10b showed a solvent-dependent shift of the fluorescence maximum wavelength in the presence of PR LBD. These results indicate that 6-arylcoumarin will be a useful scaffold for PR antagonists and fluorescent probes targeting PR. 相似文献
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本实验中大鼠妊娠第三天(D_3)出现血浆孕酮含量和子宫细胞胞核中孕酮受体含量显著同步升高和胞质中孕酮受体含量明显下降的现象,为D_5胚泡着床准备了必要的条件。D_6时血浆孕酮,胞质和胞核中孕酮受体以及子宫重量均升高,标志胚泡着床后的生理变化。 相似文献
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Identification of functional binding sites for progesterone in rat Leydig cell plasma membrane. 总被引:4,自引:0,他引:4
Steroid hormones influence cell functions by binding to intracellular receptors and then acting within the nucleus. There is now evidence that steroids affect cell functions also via interaction with plasma membrane receptors in a number of different cell types. In this regard, progesterone appears to be one of the most active steroids. In this paper, we evaluate the effects of progesterone on rat Leydig cell functions, determining variations of ion homeostasis and testosterone production. This steroid was able to effect a depolarization of the plasma membrane that was due to an influx of sodium (Na+) from the external medium since it was absent when extracellular Na+ was iso-osmotically substituted with choline chloride or sucrose. The determination of intracellular sodium concentration ([Na+]i) with the Na+ -sensitive fluorescent dye sodium-benzofuran-isophtalate (SBFI) confirmed these observations. Progesterone did not modify Leydig cell intracellular calcium concentration ([Ca2+]i) at any dose tested. Furthermore, using a cell impermeant progesterone conjugate, we demonstrated that progesterone was able to stimulate Leydig cell steroidogenesis in a dose-dependent manner. The exclusion of calcium (Ca2+) from the extracellular medium did not modify the depolarizing action of progesterone and its steroidogenetic effect while in Na+ -free medium (sucrose supplemented) progesterone-stimulated effects were completely blunted. Finally, using fluorescence microscopy with a fluorescein isothiocyanate-coupled cell impermeant progesterone conjugate, we identified plasma membrane binding sites for progesterone in rat Leydig cells. These results suggest that rat Leydig cells possess progesterone receptors located on the plasma membrane, which when occupied achieves a plasma membrane depolarization, dependent on an influx of Na+ from the external medium, and the subsequent activation of steroidogenesis. 相似文献
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Immunologic analysis of human breast cancer progesterone receptors. 2. Structure, phosphorylation, and processing 总被引:5,自引:0,他引:5
L L Wei P L Sheridan N L Krett M D Francis D O Toft D P Edwards K B Horwitz 《Biochemistry》1987,26(19):6262-6272
We have used a monoclonal antibody (MAb) directed against chick oviduct progesterone receptors (PR), that cross-reacts with human PR, to analyze PR structure and phosphorylation. This MAb, designated PR-6, interacts only with B receptors (Mr 120,000) of T47D human breast cancer cells; it has no affinity for A receptors (Mr 94,000) or for proteolytic fragments from either protein. The antibody immunoprecipitates native B receptors and was used to study the structure of native untransformed 8S and transformed 4S receptors, using sucrose density gradient analysis, photoaffinity labeling, and gel electrophoresis. On molybdate-containing low-salt gradients, PR-6 complexes with 8S B receptors, causing their shift to the bottom of the gradient while A receptors remain at 8 S. Therefore, A and B receptors form separate 8S complexes, and we conclude that A and B do not dimerize in the holoreceptor. Similar gradient studies using salt-containing, molybdate-free buffers show that there are two forms of salt-transformed 4S receptors, comprising either A proteins or B proteins, suggesting that A and B are also not linked to one another in transformed PR. The independence of A- and B-receptor complexes was confirmed by the finding that purified, transformed B receptors bind well to DNA-cellulose. Since PR-6 cross-reacts with nuclear PR, it was used to analyze nuclear PR processing--a down-regulation step associated with receptor loss as measured by hormone binding. Insoluble nuclear receptors and soluble cytosol receptors were measured by immunoblotting following treatment of T47D cells for 5 min to 48 h with either R5020 or progesterone. From 8 to 48 h after R5020 treatment, immunoassayable receptors decreased in nuclei and were not recovered in cytosols. Nuclear receptors also decreased after progesterone treatment but replenished in cytosols between 8 and 24 h after the start of treatment. Thus, processing involves a true loss of nuclear receptor protein, and not just loss of hormone binding activity, and occurs after progesterone or R5020 treatment. This loss is chronic, however, only in R5020-treated cells. Additional studies focused on the covalent modifications of receptors. We previously described shifts in apparent molecular weight of nuclear PR following R5020 treatment using in situ photoaffinity labeling. To show whether these shifts can be explained by receptor phosphorylation, untreated cells and hormone-treated cells were metabolically labeled with [32P]orthophosphate, and the B receptors were isolated by immunoprecipitation with PR-6 and analyzed by sodium dodecyl sulfate (SDS) gel electrophoresis.(ABSTRACT TRUNCATED AT 400 WORDS) 相似文献
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Steroid receptors in canine endometrial cells can be regulated by estrogen and progesterone under in vitro conditions 总被引:2,自引:0,他引:2
The expression of estrogen (ER) and progesterone receptors (PR) in the endometrium is regulated by steroid hormones. An increase in plasma estrogen leads to upregulation of the number of both steroid receptors, whereas a decrease in both receptors population is due to high concentration of plasma progesterone. To study the exact effect of different concentrations of beta-estradiol and progesterone on canine epithelial and stromal endometrial cells an in vitro model from dog uterus was developed and kept for 20 days. Material was obtained from healthy dogs, undergoing ovariohysterectomy. Endometrial epithelial and stromal cells were gained after collagenase treatment, followed by filtration steps. Electron microscopy and immunolabeling were used to study cell morphology and differentiation. Immunocytochemistry was used to determine proliferation rate (Ki-67), ER and PR status on Days 3, 8, 10, 13, and 20. Mitotic activity of both cells was stimulated with different concentrations of steroids and revealed high values until cells reached confluency. ER and PR expression in confluent layer from epithelial and stromal cells was upregulated with beta-estradiol. In addition progesterone significant downregulated both receptors population in stromal cells, whereas the reduction was less pronounced in epithelial cells. Results showed that our in vitro system is a useful tool to study the influence of beta-estradiol and progesterone on cell proliferation rate, ER and PR expression. The primary cell culture model helps to avoid experiments on living animals. 相似文献
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Zhang P Terefenko EA Fensome A Wrobel J Winneker R Zhang Z 《Bioorganic & medicinal chemistry letters》2003,13(7):1313-1316
The functional activity of 6-aryl benzoxazinone-based progesterone (PR) antagonists changed to PR agonism when the 2-carbonyl group was replaced by a 2-thiocarbonyl moiety. Based on this finding novel 6-aryl benzoxazine-2-thiones were synthesized and evaluated as PR agonists in various in vitro and in vivo assays. Several analogues had sub-nanomolar in vitro potency and showed excellent oral activities in rats. Compounds 15 and 29 had similar potencies to medroxyprogesterone acetate (MPA) in the in vitro T47D alkaline phosphatase assay and in vivo rat decidualization model. In contrast to MPA, 29 was highly selective (>500-fold) for PR over glucocorticoid and androgen receptors. 相似文献