Physiological and behavioral effects of coniferyl benzoate on avian reproduction

Various plant secondary metabolites related to cinnamic acid are of interest because of their repellency to birds and their occurrence in ecologically important food items. Coniferyl benzoate (CB), a phenylpropanoid ester that occurs in quaking aspen (Populus tremuloides) is of particular ecological interest because of its effect on ruffed grouse (Bonasa umbellus) feeding behavior and its possible influence on the population dynamics of this bird. During detoxification processes, CB and other analogous compounds are metabolized into by-products, such as ferulic acid (FA), that can cause anti-reproductive effects. We tested whether consumption of CB produces antire-productive effects similar to FA using male and female Japanese quail (Coturnix coturnix) as avian models for ruffed grouse. The parameters we investigated included: the production, morphology, and development of eggs; reproductive characteristics influenced by estrogen; serum prolactin levels; and male reproductive behavior. Dietary CB did not produce antireproductive effects similar to FA at intake levels that Japanese quail and ruffed grouse would freely consume. Consumption of CB by Japanese quail significantly reduced egg production and body mass but did not affect male reproductive performance. Coniferyl benzoate's effect on egg production may be explained by lower energy acquisition and retention rather than endocrine changes per se. Contrary to previous reports, it is unlikely that FA, or similar compounds act directly as estrogen mimics or antagonists. Although, CB did reduce egg production in quail, it is unlikely that it would affect egg production in wild ruffed grouse. Detoxification costs and the effects of CB on nutrient utilization may explain why ruffed grouse avoid high dietary levels of CB.     

Is Melanoma Progression Affected by Thyroid Diseases?

Clinical and epidemiological evidence indicate a relationship between thyroid diseases and melanoma. In particular, the hypothyroidism condition appears to promote melanoma spread, which suggests a protective role of thyroid hormones against disease progression. In addition, experimental data suggest that, in addition to thyroid hormones, other hormonal players of the hypothalamic–pituitary–thyroid (HPT) axis, namely the thyrotropin releasing hormone and the thyrotropin, are likely to affect melanoma cells behavior. This information warrants further clinical and experimental studies in order to build a precise pattern of action of the HPT hormones on melanoma cells. An improved knowledge of the involved molecular mechanism(s) could lead to a better and possibly personalized clinical management of these patients.     

Immunofluorescent Evidence for Nuclear Localization of Aromatase in Astrocytes in the Rat Central Nervous System

Estrogens regulate a variety of neuroendocrine, reproductive and also non-reproductive brain functions. Estradiol biosynthesis in the central nervous system (CNS) is catalyzed by the enzyme aromatase, which is expressed in several brain regions by neurons, astrocytes and microglia. In this study, we performed a complex fluorescent immunocytochemical analysis which revealed that aromatase is colocalized with the nuclear stain in glial fibrillary acidic protein (GFAP) positive astrocytes in cell cultures. Confocal immunofluorescent Z-stack scanning analysis confirmed the colocalization of aromatase with the nuclear DAPI signal. Nuclear aromatase was also detectable in the S100β positive astrocyte subpopulation. When the nuclear aromatase signal was present, estrogen receptor alpha was also abundant in the nucleus. Immunostaining of frozen brain tissue sections showed that the nuclear colocalization of the enzyme in GFAP-positive astrocytes is also detectable in the adult rat brain. CD11b/c labelled microglial cells express aromatase, but the immunopositive signal was distributed only in the cytoplasm both in the ramified and amoeboid microglial forms. Immunostaining of rat ovarian tissue sections and human granulosa cells revealed that aromatase was present only in the cytoplasm. This novel observation suggests a new unique mechanism in astrocytes that may regulate certain CNS functions via estradiol production.     

颗粒活性炭吸附去除水中雌激素的试验研究

以自来水为试验原水,投加雌酮(E1)、雌二醇(E2)和乙炔雌二醇(EE2),考察了颗粒活性炭去除水中雌激素的效果及动力学.结果表明,活性炭吸附能快速有效地去除水中雌激素.接触10 min后,即达到吸附平衡.平衡质量浓度与雌激素起始质量浓度有关.初始质量浓度为500 ng/L时,E1、E2和EE2的去除率分别为74.7%、89.5%和82.8%.E1、E2和EE2同时存在时,活性炭对E2的吸附效果显著变差(初始质量浓度为500 ng/L时,吸附平衡质量浓度由44.65 ng/L增加到195.03 ng/L),而对E1和EE2的吸附效果没有影响.不同初始质量浓度的等温吸附数据可用Freundlich等温吸附方程来描述.     

超高效液相色谱-串联质谱法测定饮料中的4种环境类雌激素

目的建立超高效液相色谱-串联质谱(ultra performance liquid chromatography-tandem mass spectrometry,UPLC-MS/MS)测定饮料中双酚A(bisphenol A,BPA)、双酚S(bisphenol S,BPS)、辛基酚(octylphenol,OP)和壬基酚(nonylphenol,NP)残留量的分析方法。方法样品经过HLB固相萃取柱净化后,用ZORBAX SB-Aq柱(3.0 mm×100 mm,1.8μm)分离,以甲醇和5 mmol/L乙酸铵溶液作为流动相进行梯度洗脱,电喷雾负离子模式(ESI-)电离,多反应监测模式(multiple reaction monitoring,MRM)进行检测。结果 BPA、BPS在2~100μg/L范围内线性关系良好(r0.999),方法的检出限(S/N=3)为0.3、0.01μg/L,在0.25、2、8μg/L添加水平的回收率分别为78.6%~88.0%,相对标准偏差(n=6)为1.1%~6.0%;OP、NP在10~500μg/L范围内线性关系良好(r0.999),方法的检出限(S/N=3)为0.7、0.9μg/L,在1.25、10、40μg/kg添加水平的回收率分别为85.5%~107%,相对标准偏差(n=6)为2.1%~6.6%。结论该方法简单、灵敏、准确可靠,适用于饮料中BPA、BPS、OP和NP等环境类雌激素的测定。     

Synthesis of 16-Epiestriol and its Radiolabeling Procedure

To explore novel synthetic routes of 16-epiestriol (Estra-1, 3, 5(10)-triene-3, 16β, 17β-triol), we used the estrone as the starting material. After some simple synthetic steps, 16-epiestriol was yielded. Identification and purity of intermediates in the synthetic routes were characterized by melting point and ¹H NMR spectrum analysis, respectively. In addition, the structure of 16-epiestriol was modified and radiolabeled with¹⁸F-fluoride to yield¹⁸F-FES. The corresponding quality control analysis of the injection were performed. The yield of two synthetic routes of 16-epiestriol were about 20% starting from estrone. Radiosynthesis of¹⁸F-FES was finished in 60 minutes with a radiochemical yield of (30±4)% and radiochemical purity greater than 99%. The¹⁸F-FES injection was colorless and clear and the pH value was 6.5-7.5. The specific activity of the injection saline was (1.75±0.25) Ci/μmol. In this study, 16-Epiestriol was yielded with a relatively high yield in two novel routes.¹⁸F-FES was finally yielded after structure modification of 16-epiestriol and the corresponding radiolabeling procudure. The quality control results of the¹⁸F-FES injection could meet the need in clinical examination.     

Estrogen Receptors Mediated Negative Effects of Estrogens and Xenoestrogens in Teleost Fishes—Review

Estrogen receptors (ERs) play a key role in many biochemical and physiological processes, that are involved in maintaining organism homeostasis. At the most basic level, they can be divided into nuclear estrogen receptors and membrane estrogen receptors that imply their effect in two ways: slower genomic, and faster non-genomic. In these ways, estrogens and xenoestrogens can negatively affect animal health and welfare. Most of the available literature focuses on human and mammalian physiology, and clearly, we can observe a need for further research focusing on complex mutual interactions between different estrogens and xenoestrogens in aquatic animals, primarily fishes. Understanding the mechanisms of action of estrogenic compounds on the ERs in fishes and their negative consequences, may improve efforts in environmental protection of these animals and their environment and benefit society in return. In this review, we have summarized the ER-mediated effects of xenoestrogens and estrogens on teleost fishes metabolism, their carcinogenic potential, immune, circulatory, and reproductive systems.     

Caveolin-1 Regulation and Function in Mouse Uterus during Early Pregnancy and under Human In Vitro Decidualization

Decidualization is essential to rodent and primate pregnancy. Senescence is increased during decidualization. Failure of senescence clearance during decidualization will cause pregnancy abnormality. Caveolin-1 is located in plasmalemmal caveolae and involved in senescence. However, whether caveolin-1 is involved in decidualization remains undefined. In this study, we examined the expression, regulation and function of Caveolin-1 during mouse early pregnancy and under mouse and human in vitro decidualization. From days 1 to 8 of pregnancy, Caveolin-1 signals are mainly located in endothelium and myometrium. Estrogen stimulates Caveolin-1 expression in endothelium. Deficiency of estrogen receptor α significantly promotes Caveolin-1 level in uterine stromal cells. Progesterone upregulates Caveolin-1 expression in luminal epithelium. During mouse in vitro decidualization, Caveolin-1 is significantly increased. However, Caveolin-1 is obviously decreased during human in vitro decidualization. Caveolin-1 overexpression and siRNA suppress and upregulate IGFBP1 expression under in vitro decidualization, respectively. Blastocysts-derived tumor necrosis factor α (TNFα) and human Chorionic Gonadotropin (hCG) regulate Caveolin-1 in mouse and human decidual cells, respectively. Caveolin-1 levels are also regulated by high glucose and insulin. In conclusion, a low level of Caveolin-1 should be beneficial for human decidualization.     

Premarin Reduces Neurodegeneration and Promotes Improvement of Function in an Animal Model of Spinal Cord Injury

Spinal cord injury (SCI) causes significant mortality and morbidity. Currently, no FDA-approved pharmacotherapy is available for treating SCI. Previously, low doses of estrogen (17β-estradiol, E2) were shown to improve the post-injury outcome in a rat SCI model. However, the range of associated side effects makes advocating its therapeutic use difficult. Therefore, this study aimed at investigating the therapeutic efficacy of Premarin (PRM) in SCI. PRM is an FDA-approved E2 (10%) formulation, which is used for hormone replacement therapy with minimal risk of serious side effects. The effects of PRM on SCI were examined by magnetic resonance imaging, immunofluorescent staining, and western blot analysis in a rat model. SCI animals treated with vehicle alone, PRM, E2 receptor antagonist (ICI), or PRM + ICI were graded in a blinded way for locomotor function by using the Basso–Beattie–Bresnahan (BBB) locomotor scale. PRM treatment for 7 days decreased post-SCI lesion volume and attenuated neuronal cell death, inflammation, and axonal damage. PRM also altered the balance of pro- and anti-apoptotic proteins in favor of cell survival and improved angiogenesis and microvascular growth. Increased expression of estrogen receptors (ERs) ERα and ERβ following PRM treatment and their inhibition by ER inhibitor indicated that the neuroprotection associated with PRM treatment might be E2-receptor mediated. The attenuation of glial activation with decreased inflammation and cell death, and increased angiogenesis by PRM led to improved functional outcome as determined by the BBB locomotor scale. These results suggest that PRM treatment has significant therapeutic implications for the improvement of post-SCI outcome.     

Cytotoxic Triosmium Carbonyl Clusters: A Structure–Activity Relationship Study

A structure–activity relationship (SAR) study of the triosmium carbonyl cluster Os₃(CO)₁₀(NCCH₃)₂ was carried out with a series of clusters of the general formula Os₃(CO)_12?nL_n, cationic osmium clusters and a hemi‐labile maltolato‐Os cluster. The SAR results showed that good solubility in DMSO and at least one vacant site are required for cytotoxicity. In vitro evaluation of these new compounds showed that some are selectively active against estrogen receptor (ER)‐independent MDA‐MB‐231 breast cancer cell lines relative to ER‐dependent MCF‐7 breast cancer cells, suggesting that the compounds have a different biological target specific to MDA‐MB‐231 cells. In particular, the maltolato cluster exhibits strong antiproliferative activity, with an IC₅₀ value of 3 μM after only 24 h incubation. Additionally, biochemical assays conducted with the cationic cluster show that it induces apoptosis, although a biological target has not yet been identified. Further research to establish the molecular targets of these compounds and to develop improved organometallic clusters as potential breast cancer therapeutics is underway.