改进型重组基因酵母TR-GRIP1检测化合物甲状腺激素干扰活性

应用酵母双杂交技术构建重组TR(甲状腺激素受体)基因酵母,用以检测类/抗甲状腺激素化合物及环境样品的甲状腺激素干扰活性. 提取并纯化含有TR基因的酵母表达质粒pGBT9-TR以及含有TR共激活因子GRIP1基因的酵母表达质粒pGAD424-GRIP1,将pGBT9-TR和pGAD424-GRIP1同时转化至酵母细胞Y187,以营养缺陷型培养基(SD/-Trp/-Leu)筛选阳性菌落,构建TR-GRIP1双杂交酵母. 考察该酵母与天然甲状腺激素——T₃(三碘甲状腺原氨酸)的结合情况,确定最佳暴露时间,建立剂量－效应关系曲线. 结果表明:TR-GRIP1双杂交酵母能够与T₃结合诱导β-半乳糖苷酶活性,选择暴露时间为2 h,T₃诱导酶活性的EC₅₀值为1.1×10-7 mol/L;构建的重组基因酵母TR-GRIP1提供了检测化合物甲状腺激素干扰活性的新方法.      

EEDs对鱼类性激素合成途径干扰作用研究进展

环境内分泌干扰物(environmental endocrine disruptors,EEDs)是一类可以改变生物体内激素的合成、释放、运输、代谢、结合、作用或清除等一系列生物过程的外源物质。性激素的生物合成需要一系列酶的参与,体内和体外研究表明,性激素合成途径中的类固醇生成酶是EEDs通过非性激素受体介导途径发挥内分泌扰乱作用的重要靶点,性激素合成途径的扰乱可能导致生物体生殖系统受损。本文综述了EEDs对鱼类性激素合成底物和类固醇生成酶的影响、信号转导机制及其生殖危害;并对性激素合成途径中促性腺激素调控机理、多种转录因子间的相互作用、不同物种间类固醇生成酶的差异以及各内分泌轴线的相互作用研究进行了展望,以期为EEDs通过非性激素受体介导途径发挥内分泌干扰效应的机制研究提供思路。     

Effect of anti-juvenile hormone agent,KK-42 on the incorporation rate of radioactive glycine and biosynthesis of silk proteins of silkworm,Bombyx mori L.

The effects of anti-juvenile hormone agent, KK-42 on incorporation rate of radioactive glycine in cocoon crop production and biosynthesis of silk proteins of silkworm, Bombyx mori L. were studied in a popular bivoltine silkworm hybrid, Xinhang (Chinese) × Keming (Japanese). Administration of KK-42 on first day larvae of fourth instar induced 100% trimolters, and the total larval duration was shortened by four days, which has marked advantages in sericulture. The impact of KK-42 on enhanced incorporation rate of radioactive glycine, cocoon weight, RNA content, and fibroin content was significant compared to control, which leads to superior quality of silk. This has a significant economic importance in the reeling industry.     

The effects of bisphenol A on sex hormone levels of F0 female rats and F1 male rats during weaning period

The effects of bisphenol A (BPA) were examined on sex hormones of F1 generation male rats during weaning period. Female rats were exposed to BPA from day 0 after pregnancy to the weaning period at doses of 50, 100, or 200 mg kg^?1. The sex hormone levels of F1 generation male rats were determined. This study shows that F0 generation female rats fed with 200 mg kg^?1 BPA had a significantly higher serum prolactin (PRL) levels at the end of weaning. Significantly higher levels of serum estradiol (E₂) were also found in female rats fed 100 or 200 mg kg^?1 BPA. Serum levels of E₂ in F1 male generation rats were higher in treatment groups compared to control groups while serum testosterone (T) levels were lower. Follicle stimulating hormone (FSH) in F1 generation rats fed 200 mg kg^?1 was markedly decreased. The relative testicular weights were significantly less in 100 and 200 mg kg^?1 BPA groups. BPA was found to alter the sex hormone levels in F1 male rats during weaning period and thus disrupted endocrine functions.     

Time-dependent effects of pentabrominated diphenyl ethers on gonadal hormone and genital system histology in male rats

The aim of this study was to examine the effects of pentabrominated diphenyl ethers (PBDE) on gonadal hormone levels and histology in male rats. Rats in treatment groups were orally gavaged with PBDE-99 at a dose of 120 mg?kg^?1 for 5, 15, 30, or 45 days, while controls received equal volume of corn oil. In the treated groups, changes were not found on day 5. On day 15, testicular weight increased, serum levels of estradiol (E₂) decreased, proliferation cell nuclear antigen (PCNA) positive expression was reduced, and sperms within the seminiferous tubules were damaged. On day 30, testicular weight was further increased, serum levels of testosterone (T) and E₂ decreased, PCNA positive expression was further reduced, some primary spermatocytes cells did not express, and seminiferous epithelium was degenerated. At 45 days, testicular weight decreased, levels of T, E₂ concentrations were lower, histopathologic examination revealed severe degeneration of seminiferous epithelium, and only a part of spermatogonial cells were expressed. The earliest alterations occurred at 15 days. PBDE-99 produced time-dependent reduction of gonadal hormone levels and degeneration of gonadal system histology.     

辐射化学在环境激素研究中的应用

环境激素对地球生态系统带来严重威胁.大量难降解环境激素(如多氯联苯、二噁英)危害全球脆弱的生态环境,其直接后果之一就是人类乳腺癌等恶性疾病发病率急剧上升.因此,当今世界各国均十分重视环境激素的环境生物学机理研究.辐射化学作为一门高新技术,在环境激素污染物处理、降解机理与生命科学研究等方面可发挥重要作用,例如:同步辐射可用于直接观测溶液口的雌激素受体ER真实结构,脉冲辐解、激光光解和电子自旋共振用于研究环境激素活性瞬态粒子动力学等等.     

Validation of I ecological transfer models and thyroid dose assessments using Chernobyl fallout data from the Plavsk district, Russia

Within the project “Environmental Modelling for Radiation Safety” (EMRAS) organized by the IAEA in 2003 experimental data of ¹³¹I measurements following the Chernobyl accident in the Plavsk district of Tula region, Russia were used to validate the calculations of some radioecological transfer models. Nine models participated in the inter-comparison. Levels of ¹³⁷Cs soil contamination in all the settlements and ¹³¹I/¹³⁷Cs isotopic ratios in the depositions in some locations were used as the main input information. 370 measurements of ¹³¹I content in thyroid of townspeople and villagers, and 90 measurements of ¹³¹I concentration in milk were used for validation of the model predictions.A remarkable improvement in models performance comparing with previous inter-comparison exercise was demonstrated. Predictions of the various models were within a factor of three relative to the observations, discrepancies between the estimates of average doses to thyroid produced by most participant not exceeded a factor of ten.     

Insights into the structure of urea-like compounds as inhibitors of the juvenile hormone epoxide hydrolase (JHEH) of the tobacco hornworm Manduca sexta: analysis of the binding modes and structure-activity relationships of the inhibitors by docking and CoMFA calculations

Substituted urea compounds are well-known as potent inhibitors of juvenile hormone epoxide hydrolase (JHEH) of the tobacco hornworm Manduca sexta. Docking simulations of 47 derivatives inside JHEH were performed to gain insight into the structural characteristics of these complexes. The obtained orientations show a strong similitude with the observed in the known X-ray crystal structures of human soluble epoxide hydrolase (sEH) complexed with dialkylurea inhibitors. In addition, the predicted inhibitor concentration (IC₅₀) of the above-mentioned compounds as JHEH inhibitors were obtained by a quantitative structure-activity relationship (QSAR) method by using comparative molecular field analysis (CoMFA) applied to aligned dataset. The best models included steric and electrostatic fields and had adequate predictive abilities. In addition, these models were used to predict the activity of an external test set of compounds that was not used for building the model. Furthermore, plots of the CoMFA fields allowed conclusions to be drawn for the choice of suitable inhibitors.     

First-trimester maternal serum human thyroid-stimulating hormone in chromosomally normal and Down syndrome pregnancies

Maternal serum human thyroid-stimulating hormone (TSH) levels were investigated in chromosomally normal and Down syndrome pregnancies to determine whether TSH can be used as a marker for Down syndrome in the first trimester. Measurements were conducted on stored serum samples collected from 23 Down syndrome pregnancies and 115 unaffected pregnancies before chorionic villus sampling (CVS), between 9 and 11 completed weeks of pregnancy. The samples were matched for gestational age, maternal age, maternal weight and duration of storage of the serum sample. Maternal TSH concentration was slightly decreased in Down syndrome pregnancies, with a median of 0.84 multiples of the median (MoM). Maternal serum human chorionic gonadotropin (hCG) concentration was slightly elevated in Down syndrome pregnancies, with a median of 1.03 MoM. Both differences were not significant applying matched rank analysis (p=0.50 for TSH and p=0.43 for hCG). The association between TSH and hCG in unaffected pregnancies was also measured. The Spearman correlation coefficient between TSH and hCG was −0.21 which was statistically significant (p=0.02, 95% confidence interval −0.38 to −0.03). However, it was concluded that TSH is not a useful marker for distinguishing Down syndrome-affected pregnancies from normal pregnancies in the first trimester. Copyright © 2001 John Wiley & Sons, Ltd.