Abstract:
:A variety of compounds, including the selective estrogen receptor (ER) modulators tamoxifen and raloxifene, phytoestrogens such as genistein, and xenoestrogens such as bisphenol, bind to the estrogen receptor and elicit biological responses. Structural studies have linked the altered activity of compounds such as 4-hydroxytamoxifen, raloxifene, genistein, and tetrahydrochrysene, which have substantially different structures from estradiol (E2), to differences in the positioning of the critical "helix 12" within the ligand-binding domain (LBD) of the ER-ligand complex. However, subtle permutations of the E2 molecule would also be expected to modulate the pattern of responses within a cell. Forty-two ligands were constructed by the addition or relocation of double bonds, hydroxyl, keto, amino, and nitro substituents throughout the estra-l,3,5(10)-triene (estratriene) ring system. In this review, we summarize the effects of subtle changes in the estratriene molecule on the ability of the receptor complex to stimulate the growth of MCF-7 cells, or affect the expression of four estrogen-regulated genes (progesterone receptor, pS2 protein, cathepsin D, and tissue plasminogen activator), as well as undergo nuclear processing and downregulate ERalpha mRNA. The affinity of these ligands for, and mechanism of their binding with, the ERalpha have been measured, along with their effect on the conformation of the ER-ERE complex. In particular, two A-ring isomers of E2, 2- and 4-hydroxyestratriene-17beta-ol, display gene selective activity within MCF-7 cells which is dependent on complex endogenous promoters, an intact AF-2 and is sensitive to the level of SRC-1. Both of these A-ring isomers function as antiestrogens. Molecular modeling of these two A-ring isomers complexed with the ER ligand-binding domain supports the idea that the conformation of the LBD is affected by subtle changes in the estratriene structure.
journal_name
Steroidsjournal_title
Steroidsauthors
Brooks SC,Skafar DFdoi
10.1016/j.steroids.2004.03.014subject
Has Abstractpub_date
2004-06-01 00:00:00pages
401-18issue
6eissn
0039-128Xissn
1878-5867pii
S0039128X04000571journal_volume
69pub_type
杂志文章,评审相关文献
STEROIDS文献大全abstract::A radioimmunoassay for the quantitation of the sum of free, glucuronidated and urine is described. The method is reliable and accurate. Using this method, urinary excretion of 16 alpha-hydroxyestrone was determined in normal men, premenopausal women, and postmenopausal women. The values were compared to the urinary ex...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(89)90144-x
更新日期:1989-01-01 00:00:00
abstract::The role played by progestogens in modulating Schwann cell pathophysiology is well established. Progestogens exert their effects in these cells through both classical genomic and non-genomic mechanisms, the latter mediated by the GABA-A receptor. However, there is evidence that other receptors may be involved. Membran...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2017.09.009
更新日期:2019-02-01 00:00:00
abstract::This review lays out the evidence for the role of E2 in homeostatic and hedonic feeding across several species. While significant effort has been expended on homeostatic feeding research, more studies for hedonic feeding need to be conducted (i.e. are there increases in meal size and enhanced motivation to natural foo...
journal_title:Steroids
pub_type: 杂志文章,评审
doi:10.1016/j.steroids.2017.11.011
更新日期:2018-05-01 00:00:00
abstract::A series of novel methyl spongoate (1) analogs has been synthesized and evaluated for their in vitro cytotoxic properties. It was found that the nature of the C-20 side chain had significant effects on their bioactivities and some analogs showed higher cytotoxicity than 1 against A549, HCT-116, HepG2, SW-1990, MCF-7 a...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2010.08.002
更新日期:2010-12-12 00:00:00
abstract::The xenobiotic receptors CAR and PXR constitute two important members of the NR1I nuclear receptor family. They function as sensors of toxic byproducts derived from endogenous metabolism and of exogenous chemicals, in order to enhance their elimination. This unique function of CAR and PXR sets them apart from the ster...
journal_title:Steroids
pub_type: 杂志文章,评审
doi:10.1016/j.steroids.2006.12.006
更新日期:2007-03-01 00:00:00
abstract::The use of the synthetic progestin medroxyprogesterone acetate (MPA) for estrus prevention in the dog can result in overproduction of growth hormone, suppression of plasma glucocorticoid levels, and the induction of mammary tumors. Proligestone (PROL) was claimed to be devoid of these unwanted side effects. In the pre...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(95)00216-d
更新日期:1996-03-01 00:00:00
abstract::A highly sensitive and specific quantification method of estrone and estradiol in human serum was described based upon the use of picolinoyl derivatization and liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS) in a positive mode. Estrogens were treated with picolinoyl chloride hydrochloride o...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2007.07.003
更新日期:2007-10-01 00:00:00
abstract::Steroidogenesis begins with the metabolism of cholesterol to pregnenolone by the inner mitochondrial membrane cytochrome P450 side-chain cleavage (P450scc) enzyme. The rate of steroid formation, however, depends on the rate of cholesterol transport from intracellular stores to the inner mitochondrial membrane and load...
journal_title:Steroids
pub_type: 杂志文章,评审
doi:10.1016/s0039-128x(96)00154-7
更新日期:1997-01-01 00:00:00
abstract::In comparison with the glucocorticoids cortisol and corticosterone, the mineralocorticoid aldosterone is a minority hormone of the mammalian adrenal cortex, and its proper function is dependent upon protective physiological mechanisms. These include a particular site of aldosterone synthesis in zona glomerulosa cells ...
journal_title:Steroids
pub_type: 杂志文章,评审
doi:10.1016/0039-128x(94)00021-4
更新日期:1995-01-01 00:00:00
abstract::The 3alpha,5alpha- and 3alpha,5beta-reduced derivatives of progesterone, deoxycorticosterone, dehydroepiandrosterone and testosterone enhance GABAergic neurotransmission and produce inhibitory neurobehavioral and anti-inflammatory effects. Despite substantial information on the progesterone derivative (3alpha,5alpha)-...
journal_title:Steroids
pub_type: 临床试验,杂志文章
doi:10.1016/j.steroids.2008.12.015
更新日期:2009-04-01 00:00:00
abstract::Ru(II) steroidal metal complexes were synthesized by the reaction of dichlorodicarbonyl ruthenium(II) [Ru(CO)2Cl2]n with Steroidal thiosemicarbazones. Coordination via the thionic sulfur and the azomethine nitrogen atom of the thiosemicarbazone to the Ru(II) metal. Steroidal thiosemicarbazone derivatives were obtained...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2017.05.001
更新日期:2017-08-01 00:00:00
abstract::Circulating levels (mean +/- SD) of estrone sulfate (E1S), estrone (E1) and estradiol-17 beta (E2) were measured in normal and cirrhotic postmenopausal women matched for body weight and age. In cirrhotic postmenopausal women, the E1S concentrations (201 +/- 46 pg/ml), while both E1 and E2 levels showed an increase (46...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(83)90022-3
更新日期:1983-05-01 00:00:00
abstract::A series of chemiluminescent 17beta-estradiol probes were synthesized. Relative equilibrium dissociation constants (K(D)) for the interaction of an anti-E(2) Fab fragment for the probes in solution were evaluated using a single E(2)-analog biosensor surface on a BIAcore surface plasmon resonance instrument. The result...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/s0039-128x(00)00091-x
更新日期:2000-06-01 00:00:00
abstract::Gypensapogenin H (GH) is a novel dammarane-type triterpenes obtained from hydrolyzate of total saponins from Gynostemma pentaphyllum and its anti-tumor activity has been studied in previous work. In this study, we report the effects of this compound on human prostate cancer cells (DU145 and 22RV-1). It significantly i...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2015.10.014
更新日期:2015-12-01 00:00:00
abstract::We investigated the modulatory effect of estriol (E(3)), an estrogen predominantly produced during human pregnancy, on the antigen-induced production of specific antibodies in female BALB/c mice, and its effect was compared with 17beta-estradiol (E(2)). Estriol (E(3)) had a very different effect than E(2) on the antig...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2007.10.012
更新日期:2008-03-01 00:00:00
abstract::Although exogenous glucocorticoids (GC) play a role in the regulation of bone marrow mesenchymal stem/stromal cells (MSCs) proliferation and differentiation, the function of endogenous GC is not well understood. The purpose of this study was to investigate the effect of the blockage of endogenous GC using RU486, an an...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2011.10.017
更新日期:2012-01-01 00:00:00
abstract::It has now been more than 30 years since the laboratory verification of the localization of estrogen in certain animal tissues. Much has been learned since that time regarding the details of this process, including the presence of specific receptors for these hormones in target tissues, the mechanism of ligand binding...
journal_title:Steroids
pub_type: 杂志文章,评审
doi:10.1016/0039-128x(93)90069-y
更新日期:1993-06-01 00:00:00
abstract::Synthesis of 3 beta,17 beta-dihydroxy-7 alpha/7 beta-(4-hydroxyphenyl)-androst-5-ene 3,17-diacetate (4 and 5, R = H) and 3 beta,17 beta-dihydroxy-7 alpha/7 beta-(4-methoxyphenyl)-androst-5-ene 3,17-diacetate (4 and 5, R = Me) have been carried out by Friedel-Crafts reaction on 3 beta,7,17 beta-trihydroxy-androst-5-ene...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(95)00007-d
更新日期:1995-06-01 00:00:00
abstract::To identify new pathways of estrogen action and novel estrogen receptor α (ERα) biomodulators, we performed high throughput screening and used follow on assays and bioinformatics to identify small molecule ERα inhibitors with a novel mode of action. These studies led to identification of rapid extranuclear activation ...
journal_title:Steroids
pub_type: 杂志文章,评审
doi:10.1016/j.steroids.2016.03.014
更新日期:2016-10-01 00:00:00
abstract::Significant changes in % free serum E2, T and P were observed during the annual cycle of the turtle. In contrast no significant changes in SHBG affinity constants (2.29-4.48 x 10(8) M-7) were found and binding capacity for estradiol 17B was between 3.47 and 3.96 x 10(-7) M except in preovulatory animals (2.00 +/- 0.25...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(88)90144-4
更新日期:1988-10-01 00:00:00
abstract::Contrary to the long-held postulate of steroid-hormone binding globulin action, these protein carriers of steroids are major players in steroid actions in the body. This manuscript will focus on our work with sex hormone binding globulin (SHBG) and corticosteroid binding globulin (CBG) and demonstrate how they are act...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2013.11.010
更新日期:2014-03-01 00:00:00
abstract::Counterfeiting and adulteration of pharmaceuticals is a prevalent problem worldwide and represents a major health risk to the population, with anabolic steroids being one of the main classes of drugs consumed and obtained from dubious sources. In this work, we propose the use of the 1H NMR technique to evaluate formul...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2018.07.002
更新日期:2018-10-01 00:00:00
abstract::Nine new steroidal glycosides, named as stauntosides C-K (2, 5, 7-10, 13, 14, and 16), along with seven known compounds (1, 3, 4, 6, 11, 12, and 15) were isolated from the 95% ethanol extract of the roots of Cynanchum stauntonii. The structures of these new compounds were elucidated on the basis of extensive spectrosc...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2012.10.007
更新日期:2013-01-01 00:00:00
abstract::A variety of progestins are available for therapeutic use. It is convenient to classify them into those related in chemical structure to progesterone or testosterone. Progestins related to progesterone can be subdivided into pregnanes and 19-norpregnanes, whereas those related to testosterone can be subdivided into th...
journal_title:Steroids
pub_type: 杂志文章,评审
doi:10.1016/j.steroids.2003.08.003
更新日期:2003-11-01 00:00:00
abstract::The full assignments of the (1)H and (13)C NMR signals of steroids bearing the 16beta,23:23,26-diepoxy side chain are provided. Differentiation of the diasterotopic H-26 pair was achieved with the aid of NOESY experiments. The main substituent and steric effects associated with this moiety and their influence on the c...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2008.01.027
更新日期:2008-07-01 00:00:00
abstract::MDL 18,962 was shown to be a highly specific, potent (Ki = 3-4 nM), enzyme-activated inhibitor of aromatase with minimal intrinsic endocrine properties. The affinity of MDL 18,962 was higher for human and baboon placental aromatase than for rhesus placental or rodent ovarian aromatase. These species differences necess...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(83)90065-x
更新日期:1987-07-01 00:00:00
abstract::4- to 8-cell mouse PIE's (preimplantation embryos) were cultured in vitro for 48 hr in media containing various concentrations of the anti-estrogen CI-628. Graded effects of the various concentrations were observed with the highest concentration (1.5 microng/ml) being 100% effective in blocking development to the blas...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/0039-128x(77)90005-8
更新日期:1977-03-01 00:00:00
abstract::It is well established that 1alpha,25-dihydroxyvitamin D(3) (1alpha,25(OH)(2)D(3)), the active metabolite of vitamin D, plays a role in regulating proliferation and differentiation of cells, in addition to its classic function in mineral homeostasis. Recent studies have also provided evidence for the involvement of 1a...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/s0039-128x(00)00154-9
更新日期:2001-03-01 00:00:00
abstract::Cell cycle regulator p21(CIP1) has controversial biological effects in breast cancer since in spite of its role as cell cycle inhibitor and promoter of cellular senescence, it also induces cell proliferation and chemoteraphy resistance. We here explored the molecular mechanisms involved in progestin regulation of p21(...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2012.11.003
更新日期:2013-06-01 00:00:00
abstract::It has been previously demonstrated that 1,25 dihydroxyvitamin D(3) (1,25-D(3)) exerts inhibitory effects in breast cancer cells. The aim of this study was to determine whether mitogen-activated protein kinase (MAPK) pathways are associated with 1,25-D(3)-induced cell death in breast cancer. We used three breast cell ...
journal_title:Steroids
pub_type: 杂志文章
doi:10.1016/j.steroids.2010.07.007
更新日期:2010-12-12 00:00:00