Disease relevance of Surestryl

• Based on previous studies of the properties of moxestrol, we hypothesized that a radiohalogenated analog of moxestrol, [125I]11 beta-methoxy-17 alpha-iodovinyl-estradiol [( 125I] MIVE2), should bind to the estrogen receptor (ER) in some ovarian adenocarcinomas (OVCA), thereby offering the potential for imaging and/or treatment of these cancers [1].
• Estrogen receptors of human endometrial cancer Ishikawa cells were found to be present in moderate amounts (160-200 fmol/mg protein), and to specifically bind moxestrol (R2858) with a very high affinity characterized by a Kd around 60 pM, when measured under equilibrium conditions [2].
• Oestradiol-17 beta, moxestrol, 2-fluoro-oestradiol and 4-fluoro-oestradiol all elicited pronounced LH surges and facilitated progesterone-triggered proceptive and lordosis behaviours.(ABSTRACT TRUNCATED AT 250 WORDS)[3]

High impact information on Surestryl

• Preincubating the estrogens with purified AFP (0.1-50 micrograms) did not affect the growth response to moxestrol but markedly decreased the response to E2 [4].
• Administration of either 0.5 micrograms of E2 or 10 ng of moxestrol (MOX) approximately doubled the uterine weight [4].
• 11beta-Methoxy-17-ethynyl-1,3,5(10)-estratriene-3,17beta-diol (moxestrol), a tag for estrogen receptor binding sites in human tissues [5].
• Mutational inactivation of three potential imperfect estrogen response elements in the PI-9 5'-flanking region had no effect on moxestrol estrogen receptor induction [6].
• Treatment of LPS-stimulated macrophages with moxestrol, an estrogen agonist, resulted in a similar inhibition, and the addition of the estrogen antagonist, tamoxifen, reversed E2 inhibition of JE/MCP-1 mRNA expression [7].

Biological context of Surestryl

• Possible direct effects of estrogens on lipolysis were studied by perfusion of a potent estrogenic analogue such as moxestrol [8].
• Radiotracers binding to estrogen receptors: I: Tissue distribution of 17 alpha-ethynylestradiol and moxestrol in normal and tumor-bearing rats [9].
• A study of the plasma kinetics and urinary excretion of Moxestrol was also performed to evaluate its metabolic clearance rate and absorption [10].
• The remaining animals received 1-mg injections of E2, P, moxestrol (Mox) or oil, and either were sacrificed 2 h later for NPR measurements or were tested 4 h later for reproductive behavior [11].
• Since the intestinal absorption of [14C] Moxestrol was not depressed in cirrhotic men, the low PRS values recorded are probably the consequence of hepatocyte dysfunction [10].

Anatomical context of Surestryl

• The cytoplasm of normal human male and female gingiva contains a receptor capable of specifically binding 17 beta-estradiol and moxestrol (R-2858) with high affinity (Kd = approximately 3.4 X 10(-10) M) and low capacity (4.5 fmol/mg protein) [12].
• These findings, together with previous clinical and pharmacological observations, strongly support the hypothesis that moxestrol exerts an antidopaminergic effect at the striatal level by decreasing dopaminergic postsynaptic transmission via mediation of the pituitary gland [13].
• Metabolism of estradiol, ethynylestradiol, and moxestrol in rat uterus, vagina, and aorta: influence of sex steroid treatment [14].
• Cytosol was passed through a microcolumn of Lipidex 1000 to remove interfering lipids and incubated with [3H]Moxestrol (4 nM) in the presence or absence of 500 nM Moxestrol [15].
• Scatchard plot analyses were linear, suggesting a single class of high affinity binding sites for the synthetic estrogen, R-2858 (Moxestrol) with a Kd of 5.88 X 10(-10) mol/l and a concentration of binding sites of 17.0 +/- 4.4 fmol/mg cytosol protein in the epididymis [16].

Associations of Surestryl with other chemical compounds

• Sucrose gradient centrifugation carried out at 20 C results in the transformation to a 5S form of the moxestrol- as well as the estradiol-receptor complex [17].
• Musculinization and defeminization induced in female hamsters by neonatal treatment with estradiol, RU-2858, and nafoxidine [18].
• Both tamoxifen and raloxifene had an additive effect to estrogen receptor-dependent SHBG gene expression in the HepER3 cells in the presence of saturating concentrations of moxestrol [19].
• FNA samples, being contaminated by blood, [3H] R 2858 and [3H] O 2058 are appropriate tags for ER and PR respectively, giving lowest non-specific binding [20].

Gene context of Surestryl

• The synthetic estrogens, MOX and TAM, caused significant, P < 0.001, increases of 30% and 51% in SHBG secretion at 10(-7) M compared to controls [21].
• Herring gull embryo hepatocyte cultures responded with VTG mRNA induction at moxestrol concentrations of 1 nM compared with 10 nM in chicken embryo hepatocyte cultures [22].
• After 6 h for ovalbumin and 2 h for conalbumin, the induction curves diverged according to the dose of hormone administered and in correlation with the persistence of elevated nuclear oestrogen-receptor concentrations, a result confirmed with 11 beta-methoxy-17 alpha-ethynyloestradiol (R 2858), a powerful synthetic oestrogen [23].
• alpha-Fetoprotein, the estradiol-binding plasma protein (EBP), binds estradiol but not R 2858 (11beta-methoxy-17-ethynyl-estradiol) specifically [24].
• 'Specific receptor binding' of radioactively labeled products of radiolysis of the estrogen receptor ligand R 2858 (17 alpha-ethynyl-11 beta-methoxy-estradiol-17 beta) [25].

Analytical, diagnostic and therapeutic context of Surestryl

• After treatment of cells with moxestrol, a stable estrogen derivative, for 24 to 48 h, a dramatic increase in the quantities of these lipoproteins was observed both in cell extracts and in the medium [26].
• The combined treatment of rats with T and either estradiol-17 beta, estradiol-17 alpha, or moxestrol induced florid dysplasia and markedly elevated the mitotic index (MI) in affected regions of the DLP [27].
• Cell cultures were prepared from both chicken and herring gull embryos and treated with the estradiol analogue moxestrol or the organochlorine insecticide o,p'-DDT [22].
• Electrophoretic mobility shift assays (EMSAs) with promoter regions encompassing the half sites and nuclear extracts from LMH2A cells show the presence of a moxestrol-induced complex that is abolished by a polyclonal anti-ERalpha antibody [28].
• Moxestrol metabolism was studied on urine which contained 28% of administered radioactivity after i.v. or oral administration [29].

References