Lipids. 2003 Aug;38(8):847-54.
Comparison of ex vivo inhibitory effect between 2-hydroxyestradiol and its 17-sulfate on rat hepatic microsomal lipid peroxidation.
Takanashi K, Osanai Y, Kyo T, Yoshizawa I.
Hokkaido College of Pharmacy, Otaru, Hokkaido 047-0264, Japan.
Two endogenous antioxidants that are speculated to be defense substances against preeclampsia, 2-hydroxyestradiol (2-OH-E2) and its 17-sulfate, 2-hydroxyestradiol 17-sulfate (2-OH-E2-17-S), were administered to rats to compare their inhibitory effects on hepatic microsomal lipid peroxidation, and the lipid peroxides were determined in NADPH- and ascorbic acid-dependent systems. The two catechols showed a strong inhibitory effect on lipid peroxidation in both systems, and the effect was dose dependent. However, a large difference was observed in their inhibition patterns. After administration of 2-OH-E2, the effect appeared immediately and decreased gradually with time. In contrast, the effect of 2-OH-E2-17-S appeared some time after administration and persisted for a longer time. Both catechols also showed a striking difference in their dynamics. After administration, 2-OH-E2 was detected in the blood together with its metabolites, 2-methoxyestradiol and 2-methoxyestrone, and they disappeared immediately. In contrast, 2-OH-E2-17-S was present in the blood for a longer time together with its O-methylated product, 2-methoxyestradiol 17-sulfate, but disappeared from liver microsomes within 2 h after administration. The results imply no occurrence of a direct inhibition effect of 2-OH-E2-17-S.
Neurol Res. 2003 Oct;25(7):754-8.
17 Beta-estradiol suppresses AMPA-induced increases in regional cerebral O2 consumption.
Vaks YK, Weiss HR, Liu X, Chi OZ.
Heart and Brain Circulation Laboratory, Department of Physiology and Biophysics and Anesthesia, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 125 Paterson Street, Suite 3100, New Brunswick, NJ 08901-1977, USA.
We tested the hypothesis that 17 beta-estradiol would reduce the cerebral O2 consumption response resulting from glutamate receptor stimulation by alpha amino-3-hydroxy-5-methyl-isoxazole-4-propionate (AMPA). Fourteen ovariectomized rats were separated into 17 beta-estradiol (0.5 mg 21 day release pellet) and control (placebo pellet) groups to determine cerebral blood flow (14C-iodoantipyrine) and O2 consumption (microspectrophotometry). After topical cortical stimulation with 10(-3) M and 10(-4) M AMPA, cerebral blood flow increased significantly in both groups in a concentration-dependent manner. Cerebral O2 extraction was not significantly different in any region of the 17 beta-estradiol treated group. In the placebo treated group, the O2 extraction in the saline treated cortex and in the 10(-3) M AMPA treated cortex was significantly higher when compared to the 10(-4) M AMPA treated cortex. Cerebral O2 consumption in the control group increased by 20%, from 5.2 +/- 0.6 to 6.1 +/- 0.7, with 10(-4) M AMPA and significantly increased by 64% to 8.5 +/- 0.8 ml O2 min-1 100 g-1 with 10(-3) M AMPA. The 17 beta-estradiol group demonstrated no statistically significant difference in O2 consumption between the saline treated and AMPA treated cortex. Thus, 17 beta-estradiol reduced the effects of AMPA in increasing cerebral O2 consumption.
Mol Cell Endocrinol. 2003 Oct 31;208(1-2):1-10.
Estrogen inhibits cell cycle progression and retinoblastoma phosphorylation in rhesus ovarian surface epithelial cell culture.
Wright JW, Stouffer RL, Rodland KD.
Oregon Regional Primate Research Center, Division of Reproductive Sciences, 505 NW 185th Ave, Beaverton, OR 97006, USA. wrighthsu.edu
Estrogen promotes the growth of some ovarian cancer cells at nanomolar concentrations, but has been shown to inhibit growth of normal ovarian surface epithelial (OSE) cells at micromolar concentrations (1 microg/ml). OSE cells express the estrogen receptor (ER)-alpha, and are the source of 90% of ovarian cancers. The potential sensitivity of OSE cells to estrogen stresses the importance of understanding the estrogen-dependent mechanisms at play in OSE proliferation and transformation, as well as in anticancer treatment. We investigated the effects of estradiol on cell proliferation in vitro, and demonstrate an intracellular locus of action of estradiol in cultured rhesus ovarian surface epithelial (RhOSE) cells. We show that ovarian and breast cells are growth-inhibited by micromolar concentrations of estradiol, and that this inhibition correlates with estrogen receptor expression. We further show that normal rhesus OSE cells do not activate ERK or Akt in response to estradiol, nor does estradiol block the ability of serum to stimulate ERK or induce cyclin D expression. Contrarily, estradiol inhibits serum-dependent retinoblastoma protein (Rb) phosphorylation and blocks DNA synthesis. This inhibition does not formally arrest cells, and is reversible within hours of estrogen withdrawal. Our data are consistent with growth inhibition by activation of Rb and indicate that sensitivity to hormone therapy in anticancer treatment can be modulated by cell cycle regulators downstream of the estrogen receptor.
Estradiol prevents amyloid-beta peptide-induced cell death in a cholinergic cell line via modulation of a classical estrogen receptor.
Marin R, Guerra B, Hernandez-Jimenez JG, Kang XL, Fraser JD, Lopez FJ, Alonso R.
Laboratory of Cellular Neurobiology, Department of Physiology, University of La Laguna, School of Medicine, 38071 Santa Cruz de Tenerife, Spain.
The pathology of Alzheimer's disease includes amyloid-beta peptide aggregation that contributes to degeneration of cholinergic neurons. Even though the underlying molecular mechanisms remain unclear, recent in vitro evidence supports a protective role for estrogens against several neurotoxic agents. Here we report that, in a murine cholinergic cell line (SN56), the massive cell death induced by 1-40 fragment of amyloid-beta peptide was prevented by 17beta-estradiol through a mechanism that may involve estrogen receptor activation. The protective effect of estradiol was observed in a dose-dependent manner, and was completely blocked by the pure antiestrogen ICI 182,780. In contrast, the inactive isomer 17alpha-estradiol consistently showed weaker neuroprotection than the native hormone that was unaffected by ICI 182,780 treatment. In addition, equivalent concentrations of 17beta-estradiol enhanced luciferase activity in cells transfected with a luciferase reporter gene driven by tandem estrogen response elements. Estrogen-induced luciferase activity was blocked by ICI 182,780, indicating estrogen receptor-dependent transcriptional activity. We also observed by reverse transcription-polymerase chain reaction, Western blot and immunocytochemistry that increasing concentrations of 17beta-estradiol enhanced the expression of estrogen receptor alpha mRNA and protein during amyloid-beta-induced toxicity. Under these conditions, it was found by confocal microscopy that the localization of estrogen receptor alpha in the absence of hormone was mainly extranuclear. However, the receptor was consistently obse
beta-estradiol influences differentiation of hippocampal neurons in vitro through an estrogen receptor-mediated process.
Audesirk T, Cabell L, Kern M, Audesirk G.
Biology Department, University of Colorado at Denver, PO Box 173364, Denver, CO 80217-3364, USA. taudesiarbon.cudenver.edu
We utilized morphometric analysis of 3 day cultures of hippocampal neurons to determine the effects of both estradiol and the synthetic estrogen receptor modulator raloxifene on several parameters of neuronal growth and differentiation. These measurements included survival, neurite production, dendrite number, and axon and dendrite length and branching. 17 beta-Estradiol (10 nM) selectively stimulated dendrite branching; this effect was neither mimicked by alpha-estradiol, nor blocked by the estrogen receptor antagonist ICI 182780. The selective estrogen receptor modulator raloxifene (100 nM) neither mimicked nor reversed the effects of estradiol on dendritic branching. Western immunoblotting for the alpha and beta subtypes of estrogen receptor revealed the presence of alpha, but not beta, estrogen receptors in our hippocampal cultures. There is growing recognition of the effects of 17 beta-estradiol on neuronal development and physiology, with implications for brain sexual dimorphism, plasticity, cognition, and the maintenance of cognitive function during aging. The role of estradiol in hippocampal neuronal differentiation and function has particular implications for learning and memory. These data support the hypothesis that 17 beta-estradiol is acting via alpha estrogen receptors in influencing hippocampal development in vitro. Raloxifene, prescribed to combat osteoporosis in post-menopausal women, is a selective estrogen receptor modulator with tissue-specific agonist/antagonist properties. Because raloxifene had no effect on dendritic branching, we hypothesize that it does not interact with the alpha estrogen receptor in this experimental paradigm.
J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Nov 5;796(2):267-81.
Analysis of the progesterone displacement of its human serum albumin binding site by beta-estradiol using biochromatographic approaches: effect of two salt modifiers.
Andre C, Jacquot Y, Truong TT, Thomassin M, Robert JF, Guillaume YC.
Equipe des Sciences Separatives et Biopharmaceutiques (2SB), Laboratoire de Chimie Analytique, Place Saint-Jacques, 25030 Besancon Cedex, France.
The mechanisms of (i) the binding of two sex-hormones (i.e. progesterone and beta-estradiol) to human serum albumin (HSA) and (ii) the progesterone displacement of its HSA binding cavity by beta-estradiol were studied by biochromatography using three different methods. In the first time, zonal elution method was used to prove the direct competition effect between the two sex-hormone. In the second time, the competition effect between beta-estradiol and progesterone to bound on the same HSA site was analysed by the competitive bi-Langmuir approach. Finally, the thermodynamic data of these two binding processes were studied. The Gibbs free energy value (Delta(approximately)G degrees) of the displacement equilibrium was negative demonstrating that beta-estradiol displaced progesterone of its HSA binding cavity. Moreover, the effect of two chloride modifiers (i.e. Na(+), Mg(2+)) on these two binding processes were analysed. Results showed that in the salt biological concentration ranges, the Mg(2+) cation enhanced strongly the bioavailable progesterone, whereas the Na(+) cation interacted slowly on the progesterone displacement of its HSA binding site by beta-estradiol. This study showed that it must be useful to carry out more in vivo test on the magnesium supplementation effect for women who suffer from estrogen dominance syndrome.
Am J Obstet Gynecol. 2003 Oct;189(4):1080-4.
Endocrine assessment of relative reproductive age in normal eumenorrheic younger and older women across multiple cycles.
Jain T, Klein NA, Lee DM, Sluss PM, Soules MR.
Division of Reproduction Endocrinology and Infertility, Department of Obstetrics and Gynecology, University of Washington Medical Center, Seattle, USA. tjaiartners.org
OBJECTIVE: The aim of this study was to better characterize the ranges and intercycle variability for day 3 follicle-stimulating hormone, estradiol, and inhibin B levels in normal eumenorrheic women. STUDY DESIGN: Healthy eumenorrheic volunteers were recruited, of whom 27 women were 20 to 25 years old (peak reproductive age) and 36 women were 40 to 45 years old (study population). Blood samples were obtained on day 3 of two consecutive menstrual cycles. In some women, an additional blood sample on day 3 was obtained within 1 year. RESULTS: In normal women aged 20 to 25 years versus women aged 40 to 45 years, the day 3 follicle-stimulating hormone geometric mean is 5.6 IU/L (95% CI, 3.3-9.5 IU/L) versus 9.6 IU/L (95% CI, 3.8-23.8 IU/L), the day 3 estradiol geometric mean is 44.0 pg/mL (95% CI, 20.4-95.0 pg/mL) versus 52.4 pg/mL (95% CI, 22.4-122.8 pg/mL), and the day 3 inhibin B geometric mean is 100.4 pg/mL (95% CI, 51.7-195.0 pg/mL) versus 52.4 pg/mL (95% CI, 9.5-289.3 pg/mL). Furthermore, 22% of women in the older age group have a normal day 3 follicle-stimulating hormone and estradiol level in one cycle but an elevated value in a consecutive cycle (P=.008). CONCLUSION: In women of peak reproductive age, the upper limit of day 3 follicle-stimulating hormone and estradiol levels are 9.5 IU/L and 95.0 pg/mL, respectively, and the lower limit of day 3 inhibin B level is 51.7 pg/mL. If the initial day 3 follicle-stimulating hormone and estradiol levels in an older woman are normal, then a second measurement in a subsequent cycle should be obtained before counseling this woman regarding her reproductive potential.
Reprod Fertil Dev. 2003;15(5):269-74.
Steroid hormones augment nitric oxide synthase activity and expression in rat uterus.
Ogando D, Farina M, Ribeiro ML, Perez Martinez S, Cella M, Rettori V, Franchi A.
Center of Pharmacological and Botanical Studies (CEFYBO), Consejo Nacional de Investigaciones Cientificas y Tecnicas (CONICET), Serrano 669, Capital Federal, 1414 Buenos Aires, Argentina.
Nitric oxide (NO) is synthesized in a variety of tissues, including rat uterus, from L-arginine by NO synthase (NOS), of which there are three isoforms, namely neuronal, endothelial and inducible NOS (nNOS, eNOS and iNOS, respectively). Nitric oxide is an important regulator of the biology and physiology of the organs of the reproductive system, including the uterus. Some studies have shown increased variation in NO production and NOS expression during the oestrous cycle. However, the factors that regulate NO production in the uterus remain unclear. Therefore, in the present study, we investigated the effect of sex steroids on NOS expression and activity in the ovariectomized rat uterus. Ovariectomized rats received progesterone (4 mg per rat) or 17beta-oestradiol (1 micro g per rat). All rats were killed 18 h after treatment. Both progesterone and oestradiol were able to augment NOS activity. The effect of oestradiol was abolished by pre-incubation with 500 micro M aminoguanidine, an iNOS inhibitor, or by coadministration of oestradiol with 3 mg kg(-1) dexamethasone, but the effect of progesterone was not affected by these treatments. Uterine nNOS, eNOS and iNOS protein levels were assessed using Western blots. Ovariectomized rat uteri expressed iNOS and eNOS. Progesterone increased the expression of eNOS and iNOS, whereas oestradiol increased iNOS expression only. These results suggest that oestradiol and progesterone are involved in the regulation of NOS expression and activity during pregnancy and implantation in the rat.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=14588184&dopt=Abstract estradiol [PubMed - in process]
Pharmacol Biochem Behav. 2003 Sep;76(2):327-33.
Interaction between estradiol replacement and chronic stress on feeding behavior and on serum leptin.
Gamaro GD, Prediger ME, Lopes JB, Dalmaz C.
Departamento de Bioquimica, ICBS, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-ANEXO. CEP: 90035-003. Porto Alegre, Rio Grande do Sul, Brazil.
Exposure to stress may cause either an increase or a decrease in food intake. Behavioral and physiological responses to stress, including alterations in feeding behavior, are sexually dimorphic. This study aimed to evaluate the interaction between estradiol levels and chronic variate stress on the intake of sweet food and on serum levels of leptin, a hormone secreted by the adipose cells with a role in the regulation of body weight. Adult female Wistar rats were used. After ovariectomy, the animals received estradiol replacement (or oil) subcutaneously. Rats were then divided in controls and stressed (submitted to 30 days of variate stress). Consumption of sweet food and of serum leptin was measured. Although animals receiving estradiol replacement presented smaller weight gain, they showed an increased consumption of sweet food. Chronic variate stress decreased sweet food intake at 30, but not at 20, days of treatment. Estradiol replacement in the stressed group prevented both the reduction observed in sweet food intake and the increase in leptin levels. These results suggest that there is an interaction between chronic stress and estradiol replacement in feeding behavior concerning sweet food consumption, and this interaction may be related to altered leptin levels.
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