共查询到20条相似文献,搜索用时 8 毫秒
1.
2.
3.
Otto C Fuchs I Altmann H Klewer M Schwarz G Bohlmann R Nguyen D Zorn L Vonk R Prelle K Osterman T Malmström C Fritzemeier KH 《The Journal of steroid biochemistry and molecular biology》2008,111(1-2):95-100
Estrogen receptor (ER) ligands that are able to prevent postmenopausal bone loss, but have reduced activity in the uterus and the mammary gland might be of great value for hormone therapy. It is well established that the classical ER can activate genomic as well as nongenomic signal transduction pathways. In this study, we analyse the in vivo behaviour of ER ligands that stimulate nongenomic ER effects to the same extent as estradiol, but show clearly reduced activation of genomic ER effects in vitro. Using different readout parameters such as morphological changes, cellular proliferation, and target gene induction, we are able to demonstrate that ER ligands with reduced genomic activity in vitro show a better dissociation of bone versus uterine and mammary gland effects than estradiol that stimulates genomic and nongenomic effects to the same extent. We conclude that pathway-selective ER ligands may represent an interesting option for hormone therapy. 相似文献
4.
E R Levin 《Journal of applied physiology》2001,91(4):1860-1867
5.
6.
Mechanisms of genomic and non-genomic actions of carotenoids 总被引:1,自引:0,他引:1
Elliott R 《Biochimica et biophysica acta》2005,1740(2):147-154
Carotenoids are highly bioactive dietary compounds that have the potential to have significant effects on human health. It is becoming increasingly clear that the various biological effects that carotenoids exert could be driven via a number of different mechanisms. These include direct pro- and antioxidant effects, redox sensitive cell signalling, vitamin A signalling pathways and other as yet unidentified mechanisms. This article provides an overview of the known effects of carotenoids and discusses the use of model systems and functional genomic approaches further to elucidate their modes of action. 相似文献
7.
8.
9.
10.
11.
12.
膜雌激素受体介导一氧化氮合酶活性增高的快速非基因效应 总被引:13,自引:1,他引:12
实验利用新生小牛胸主动脉内皮细胞(BAECs)作为模型,观察17β-雌二醇(E2)、E2BSA对BAECs中内皮型一氧化氯合酶(eNOS)的快速激活作用,并探讨了丝裂素活化蛋白激酶(MAPK)信号通路在其中的作用。结果显示,不同浓度的E2(0.001—1lμmol/L)作用于BAECs l5 min均能快速激活eNOS;0.01μmol/L浓度的E2作用于BAECs,5min即能激活eNOS,15min达到最大效应,随后eNOS快速失活;E2BSA(17.5ng/m1)作用于BAECs,15min同样可激活eNOS。E2、E2BSA激活eNOS的作用均能被雌激素受体(ER)拮抗剂tamoxifen(0.1μmol/L)或MAPK激酶特异抑制剂PD98059(50μmol/L)所阻断。放线菌素D(25μg/ml)不能阻断E2、E2BSA对eNOS的激活作用。E2(0.01μmol/L)、E2BSA(17.5ng/ml)作用于BAECs l5 min后可明显促进p42/p44磷酸化MAPK蛋白表达,而对p42/p44 MAPK总蛋白表达无影响。Tamoxifen可部分阻断E2;E2BSA激活p42/p44磷酸化MAPK的作用。这些结果提示,BAECs膜上可能存在膜雌激素受体(membrane estrogen receptor,mER),E2、E2BSA作用于mER后可通过MAPK信号途径快速激活eNOS。 相似文献
13.
14.
Barreiro Arcos ML Sterle HA Paulazo MA Valli E Klecha AJ Isse B Pellizas CG Farias RN Cremaschi GA 《Journal of cellular physiology》2011,226(12):3208-3218
Thyroid hormones (THs) exert a broad range of actions on development, growth, and cell differentiation by both genomic and nongenomic mechanisms. THs regulate lymphocyte function, but the participation of nongenomic actions is still unknown. Here the contribution of both genomic and nongenomic effects on TH-induced division of T cells was studied by using free and noncell permeable THs coupled to agarose (TH-ag). THs-ag led to cell division, but to a lesser extent than free hormones. THs induced nongenomically the rapid translocation of protein kinase C (PKC) ζ isoform to cell membranes, extracellular-signal-regulated kinases (ERK1/2) phosphorylation and nuclear factor-κB (NF-κB) activation. The signaling cascade include sphingomyelinases acting up-stream the activation of PKCζ isoform, while ERK and NF-κB are activated downstream this PKC isoenzyme. Both free and THs-ag increased the protein and mRNA levels of TH nuclear receptor TRα1, while only free hormones incremented the inducible NOS gene and protein levels as well as a calcium independent NOS activity. Both effects were blunted by PKCζ inhibition. These results indicate that THs, by triggering a nongenomic signaling cascade that involves Smases-mediated activation of PKCζ, lead to ERK 1/2 and NF-κB activation and to the genomic increase of TRs and the inducible nitric oxide synthase protein and mRNA levels, improving T lymphocyte proliferation. These finding not only contribute to the understanding of the mechanisms involved in TH modulation of lymphocyte physiology, but would also point out for the first time the interplay between genomic and nongenomic TH actions in T cells. 相似文献
15.
16.
Narayanan R Coss CC Yepuru M Kearbey JD Miller DD Dalton JT 《Molecular endocrinology (Baltimore, Md.)》2008,22(11):2448-2465
Androgen receptor (AR) ligands are important for the development and function of several tissues and organs. However, the poor oral bioavailability, pharmacokinetic properties, and receptor cross-reactivity of testosterone, coupled with side effects, place limits on its clinical use. Selective AR modulators (SARMs) elicit anabolic effects in muscle and bone, sparing reproductive organs like the prostate. However, molecular mechanisms underlying the tissue selectivity remain ambiguous. We performed a variety of in vitro studies to compare and define the molecular mechanisms of an aryl propionamide SARM, S-22, as compared with dihydrotestosterone (DHT). Studies indicated that S-22 increased levator ani muscle weight but decreased the size of prostate in rats. Analysis of the upstream intracellular signaling events indicated that S-22 and DHT mediated their actions through distinct pathways. Modulation of these pathways altered the recruitment of AR and its cofactors to the PSA enhancer in a ligand-dependent fashion. In addition, S-22 induced Xenopus laevis oocyte maturation and rapid phosphorylation of several kinases, through pathways distinct from steroids. These studies reveal novel differences in the molecular mechanisms by which S-22, a nonsteroidal SARM, and DHT mediate their pharmacological effects. 相似文献
17.
18.
19.