雌激素及植物雌激素对去卵巢大鼠子宫组织VEGF表达和形态的影响

目的比较雌激素及植物雌激素对去卵巢大鼠子宫组织VEGF和形态表达的影响。方法48只Wistar大鼠随机分为8组:假手术组(Sham)、去卵巢组(Ovx)、17β-雌二醇组(Ovx+Est)、17-β雌二醇+黄体酮组(Ovx+Est+Pro)、黄体酮组(Ovx+Pro)、染料木素组(Ovx+Gen)、白黎芦醇组(Ovx+Res)、根皮素组(Ovx+Phl)。给药21 d,用蛋白免疫印迹法观察各组子宫VEGF的表达、并用免疫组化对VEGF的表达部位和其形态学变化进行观察。结果与Sham组比较,Ovx组的VEGF表达下调;与Ovx比较,Ovx+Est和Ovx+Est+Pro两组VEGF表达均明显上调。Gen、Res和Phl对卵巢切除大鼠VEGF无影响。大鼠卵巢切除后,子宫明显萎缩且重量下降。皮下注射Est或Est合并Pro后,子宫组织密度增加,子宫被覆上皮细胞和腺体明显增生。皮下注射Gen和Phl后,子宫形态变化类似卵巢切除大鼠,注射Res可促进去卵巢大鼠子宫腺体的增生,但作用没有雌激素强。结论雌孕激素使VEGF表达明显上调;植物雌激素Res有促进腺泡增生作用。     

槲皮素、补骨脂素对人乳腺癌T47D细胞两种受体亚型表达的影响

目的探讨槲皮素和补骨脂素的雌激素作用以及调控雌激素受体亚型表达的作用机制。方法10μmol.L-1槲皮素和10μmol.L-1补骨脂素分别处理T47D细胞48 h,采用RT-PCR和Western blot方法测定对雌激素依赖性乳腺癌细胞T47D雌激素受体亚型ERα和ERβ表达的影响,并以雌激素受体拮抗剂ICI182,780为工具药来评价槲皮素和补骨脂素发挥雌激素样作用与雌激素受体的关系。结果槲皮素、补骨脂素在10μmol.L-1可明显诱导T47D细胞ERαmRNA和蛋白表达,而对ERβ表达没有影响。当与ICI182,780共孵育T47D细胞ERα表达被拮抗。结论槲皮素、补骨脂素产生的促进ER阳性细胞增殖的雌激素样作用是通过增加ERα表达实现的。     

植物雌激素的研究进展

植物雌激素是植物中一类结构与功效类似于动物雌激素的天然杂环多酚类化合物,能够与雌激素受体亚基（ERα或ERβ）结合,发挥雌激素样或抗雌激素样作用。就植物雌激素成分的结构分类以及含植物雌激素成分的中药进行归纳总结,以期在数以千计的中药中寻找到具有雌激素样或抗雌激素样活性的新药源。     

Circulating enterolactone and risk of endometrial cancer

It has been suggested that phytoestrogens protect against hormone-dependent cancers. Lignans are the main class of phytoestrogens in Western diets. We conducted a prospective study of endometrial cancer and circulating levels of the main human lignan, enterolactone. The design was a case-control study nested within 3 prospective cohort studies, in New York, Sweden and Italy. Serum or plasma samples had been collected at enrollment and stored at -80 degrees C. A total of 153 cases, diagnosed a median of 5.3 years after blood donation, and 271 matched controls were included. No difference in circulating enterolactone was observed between cases (median, 19.2 nmol/L) and controls (18.5 nmol/L). Adjusting for body mass index, the odds ratio for the top tertile of enterolactone, as compared to the lowest was 1.2 (95% CI, 0.7-2.0; p for trend = 0.53). Lack of association was observed in both pre- and postmenopausal women. No correlation was observed between enterolactone and circulating estrogens or SHBG in healthy postmenopausal women. These results do not support a protective role of circulating lignans, in the range of levels observed, against endometrial cancer.     

Stimulatory effect of genistein and apigenin on the growth of breast cancer cells correlates with their ability to activate ER alpha

Summary Genistein and apigenin are phytoestrogens present in commercial preparations used for the treatment of postmenopausal symptoms. In this study, we assessed the influence of these compounds on mammary tumor growth. Both compounds stimulate the proliferation of MCF-7 and T47D cells [estrogen receptor alpha (ERα-positive)], but do not stimulate the proliferation of an ERα-negative cell line (MDA-MB-435 cells). Genistein appeared more efficient in this regard due to its higher binding affinity for ERα, a property explained by a structural analysis of the binding of these compounds to the ERα’s ligand binding domain. As previously described for estradiol (E₂), genistein and apigenin down regulated ERα and enhanced estrogen response element (ERE)-dependent gene expression. The additional finding that genistein antagonizes the anti-proliferative effect of hydroxytamoxifen suggests phytoestrogens may be detrimental in women with breast cancer who are being treated with tamoxifen. In addition, because of their ability to stimulate breast cell growth, the widespread use of phytoestrogens in postmenopausal women could be detrimental.     

High-density lipoproteins: effects of alcohol, estrogen, and phytoestrogens

Plasma high-density lipoproteins (HDL) play an important role in the reverse cholesterol transport pathway. Factors affecting plasma HDL levels may be important, therefore, in the prevention of cardiovascular disease. Among the lifestyle and environmental factors that have been shown to increase HDL cholesterol are moderate alcohol intake and estrogen administration. Phytoestrogens, molecules of plant origin that resemble estrogen and act as weak estrogens, do not have a clear effect on HDL cholesterol. The molecular mechanisms of action of alcohol, estrogen, and phytoestrogens on HDL are under investigation.     

Synthesis of new deuterium‐labelled lignanolactones

Deuteration of several lignanolactones, using ²H₃PO₄·BF₃/²H₂O as the deuteration reagent, is described, affording new stable isotopically pure polydeuterated lignans. All aromatic hydrogens are exchanged, including the less active ones. The order of ¹H/²H exchange is studied by comparing calculated electrostatic potential values and experimental observations. Labile deuteriums are exchanged back to hydrogens with methanolic HCl to achieve stable isotopically pure compounds. Copyright © 2008 John Wiley & Sons, Ltd.     

植物雌激素干预乳腺癌的研究进展

植物雌激素(phytoestrogen)是一类存在于植物中,与雌激素结构相近的生物活性物质,主要包括异黄酮(isoflavone),木酚素(lignan)和香豆素(coumestrol)三大类。流行病学调查发现植物雌激素摄入量增加可以降低乳腺癌和其他一些肿瘤的发病率。本研究通过对植物雌激素的来源、特性及其体内、外实验的研究的相关文献进行综述,探讨其干预乳腺癌的作用机制及其研究进展。     

Effect of rodent diets on the sexual development of the rat.

Five rodent diets have been evaluated for their possible effect on the sexual development of the rat. Groups of 12 pregnant Alpk rats were fed one of the following combinations of diets during pregnancy and postnatally: RM3/RM1, AIN-76A/AIN-76A, RM3/AIN-76A, Teklad Global 2016 (Global)/Global and Purina 5001/Purina 5001. AIN-76A is phytoestrogen-free while the other diets contained varying amounts of phytoestrogens. The phytoestrogens genistein and daidzein were determined in the diets studied, and the concentrations found agreed with earlier estimates. RM3/RM1 was selected as the control group, as this has been used routinely in this laboratory for the past decade. Determinations were made in offspring of the times of vaginal opening and first estrus among the females, and of prepuce separation and testes descent among the males. At postnatal day (PND) 26 the females from 6 of the 12 litters were terminated and tissue weights measured. Males from 6 of the 12 litters were similarly studied at PND 68. Animals from the remaining litters were transferred to RM1 diet at PND 70. Termination of the study was at PND 128 (males) and PND 140 (females) when body weights and tissue weights were determined. Marked differences in body weight, sexual development, and reproductive tissue weights were observed for rats maintained on AIN-76A or Purina 5001, with only minimal effects among rats maintained on the Global diet. These comparisons were against RM3/RM1 as the reference diet. However, using Purina 5001 as the reference diet reversed the direction of the differences seen when using RM3/RM1 as the reference diet. The differences observed when using RM3/RM1 as reference diet occurred mainly postnatally. In addition, the fact that similar differences were seen for the phytoestrogen-free diet, AIN-76A, and the phytoestrogen-rich diet, Purina 5001, indicate that these effects are more likely to be caused by nutritional differences between the diets that then have centrally mediated effects on rodent sexual development, rather than individual dietary components affecting peripheral estrogen receptors (ER). This proposal is supported by abolition of the uterotrophic activity of AIN-76A and Purina 5001 (relative to RM3/RM1) in the immature rat by coadministration of the gonadotrophin-releasing hormone (GnRH) antagonist ANTARELIX: The present data indicate that choice of diet may influence the timing of sexual development in the rat, and consequently, that when evaluating the potential endocrine toxicity of chemicals, the components of rodent diets used should be known, and as far as is possible, controlled.