Synapse. 2003 Jan;47(1):10-4.
Dehydroepiandrosterone (DHEA) such as 17beta-estradiol prevents MPTP-induced dopamine depletion in mice.
D'Astous M, Morissette M, Tanguay B, Callier S, Di Paolo T.
Molecular Endocrinology and Oncology Research Center, Laval University Medical Center (CHUL), Quebec, Qc, G1V 4G2, and Faculty of Pharmacy, Laval University, Quebec, Qc, G1K 7P4, Canada.
Previous work from our laboratory has shown prevention of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced striatal dopamine (DA) depletion in mice by 17beta-estradiol, progesterone, and raloxifene. Dehydroepiandrosterone (DHEA), a neurosteroid, was shown to have neuroprotective activities in various paradigms of neuronal death but its effect in vivo in mice on MPTP toxicity has not been reported. We investigated the effects of 17beta-estradiol (2 microg/day) and DHEA (3 mg/day) for 5 days before and after an acute treatment of four MPTP (10 mg/kg) injections in male C57Bl/6 mice. Striatal DA concentrations and its metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were measured by HPLC. MPTP mice that received 17beta-estradiol or DHEA had striatal DA, DOPAC, and HVA concentrations comparable to intact animals and higher than striatal DA, DOPAC, and HVA levels in saline-MPTP-treated mice. MPTP treatment led to an increase of striatal DA turnover (assessed with the HVA/DA ratio); DHEA and 17beta-estradiol prevented this increase. 17beta-Estradiol did not affect striatal DA and metabolites concentrations in intact mice in this paradigm. Furthermore, in the substantia nigra DHEA and 17beta-estradiol prevented the MPTP-induced dopamine transporter and tyrosine hydroxylase mRNA decreases measured by in situ hybridization. Therefore, DHEA such as 17beta-estradiol is active in preventing the catecholamine-depleting effect of MPTP and our results suggest that this involves neuroprotection of DA neurons. Copyright 2002 Wiley-Liss, Inc.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12422368&dopt=Abstract estradiol [PubMed - indexed for M
Di Yi Jun Yi Da Xue Xue Bao. 2001;21(11):844-846.
Effect of estradiol and progesterone on calcitonin expression in in vitro cultured human endometrial epithelial cells in the implantation window.
Fu ZH, Chen SL, Xing FQ.
Department of Obstetrics and Gynecology, Nangfang Hospital, First Military Medical University, Guangzhou 510515, China.
OBJECTIVE: To explore the effect of estradiol and progesterone on the expression of calcitonin in human endometrial epithelial cells cultured in vitro. METHODS: Human endometrial epithelial cells were cultured in vitro in DMEM medium. After the cells were treated respectively with estradiol and progesterone at different concentrations for 24 and 48 h, the fluorescence density of the cells was measured by flow cytometer. RESULTS: Progesterone treatment of the epithelial cells for 24 h produced in a dose-dependent manner significantly higher fluorescence level than that of the control (P<0.01). Small dose of estradiol took little effect on calcitonin expression, but high-concentration estradiol resulted in lowered fluorescence level than the control. CONCLUSION: Progesterone promotes calcitonin expression in cultured human endometrial epithelial cells in a dose-dependent manner, while estradiol tends to inhibit its expression.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12426189&dopt=Abstract estradiol [PubMed - as supplied by publisher]
Am J Physiol Regul Integr Comp Physiol. 2002 Dec;283(6):R1378-85.
Estradiol treatment increases CCK-induced c-Fos expression in the brains of ovariectomized rats.
Eckel LA, Houpt TA, Geary N.
Weill Medical College of Cornell University and E.W. Bourne Behavioral Laboratory, New York Presbyterian Hospital, Westchester Division, White Plains New York 10509, USA. eckesy.fsu.edu
The ovarian hormone estradiol reduces meal size and food intake in female rats, at least in part by increasing the satiating potency of CCK. Here we used c-Fos immunohistochemistry to determine whether estradiol increases CCK-induced neuronal activation in several brain regions implicated in the control of feeding. Because the adiposity signals leptin and insulin appear to control feeding in part by increasing the satiating potency of CCK, we also examined whether increased adiposity after ovariectomy influences estradiol's effects on CCK-induced c-Fos expression. Ovariectomized rats were injected subcutaneously with 10 microg 17beta-estradiol benzoate (estradiol) or vehicle once each on Monday and Tuesday for 1 wk (experiment 1) or for 5 wk (experiment 2). Two days after the final injection of estradiol or vehicle, rats were injected intraperitoneally with 4 microg/kg CCK in 1 ml/kg 0.9 M NaCl or with vehicle alone. Rats were perfused 60 min later, and brain tissue was collected and processed for c-Fos immunoreactivity. CCK induced c-Fos expression in the nucleus of the solitary tract (NTS), area postrema (AP), paraventricular nucleus of the hypothalamus (PVN), and central nucleus of the amygdala (CeA) in vehicle- and estradiol-treated ovariectomized rats. Estradiol treatment further increased this response in the caudal, subpostremal, and intermediate NTS, the PVN, and the CeA, but not in the rostral NTS or AP. This action of estradiol was very similar in rats tested before (experiment 1) and after (experiment 2) significant body weight gain, suggesting that adiposity does not modulate CCK-induced c-Fos expression or interact with estradiol
Cell Cycle. 2002 May-Jun;1(3):220-6.
Raf-induced cell cycle progression in human TF-1 hematopoietic cells.
Chang F, Steelman LS, McCubrey JA.
Department of Microbiology and Immunology; Brody School of Medicine at East Carolina University; Greenville, North Carolina 27858, USA. mubreyail.ecu.edu
Ras/Raf/MEK/ERK is a crucial pathway regulating cell cycle progression, apoptosis, and drug resistance. The Ras oncogene is frequently mutated in human cancer, which can result in the activation of the downstream Raf/MEK/ERK cascade leading to cell cycle progression in the absence of a growth stimulus. Raf-induced proliferation has been observed in hematopoietic cells. However, the mechanisms by which Raf affects cell cycle progression are not well described. To investigate the importance of Raf/MEK/ERK signaling in human hematopoietic cell growth, the effects of three different Raf genes, A-Raf, B-Raf and Raf-1, on cell cycle progression and regulatory gene expression were examined in TF-1 cells transformed to grow in response to beta-estradiol-regulated DeltaRaf:ER genes. Raf activation increased the expression of cyclin A, cyclin D, cyclin E, and p21(Cip1), which are associated with G(1) progression. Activated DeltaRaf-1:ER and DeltaA-Raf:ER but not DeltaB-Raf:ER increased Cdk2 and Cdk4 kinase activity. The regulatory role of p16(Ink4a), a potent Cdk4 kinase inhibitor, on the kinase activity of Cdk2 and Cdk4 was also examined. Raf induced p16(Ink4a) suppressor but this did not eliminate Cdk4 kinase activity. These results indicate that human hematopoietic cells transformed to grow in response to activated Raf can be used to elucidate the mechanisms by which various cell cycle regulatory molecules effect cell cycle progression. Furthermore, the differences that the various Raf isoforms have on Cdk4 activity and other cell cycle regulatory molecules can be determined in these cells.
Life Sci. 2002 Sep 20;71(18):2181-93.
17Beta-estradiol inhibits the adhesion of leukocytes in TNF-alpha stimulated human endothelial cells by blocking IL-8 and MCP-1 secretion, but not its transcription.
Rodriguez E, Lopez R, Paez A, Masso F, Montano LF.
Depto. Biologia Celular, Instituto Nacional de Cardiologia Ignacio Chavez, Juan Badiano 1, Tlalpan 14080, D.F., Mexico, Mexico.
Inflammation, and especially mononuclear cell adhesion to endothelium, is an important physiopathological component of atherosclerosis. Since coronary heart disease in women of reproductive age and/or with estrogen replacement therapy is reduced, our aim was to determine if 17beta-estradiol had a regulatory effect on the adhesion of lymphocytes to the endothelium. We performed U-937 cells adhesion assays in TNF-alpha-stimulated HUVECs, and we also quantitated IL-8 and MCP-1 in culture supernatants, in the presence or not of 17beta-estradiol. The presence of alpha- and beta-estrogen receptors was determined by Western blot and RT-PCR, respectively, whereas the transcription of both chemokines was evaluated by RT-PCR. The results showed a 35% decrease in the adhesion of U-937 monocyte cells to TNF-alpha-stimulated HUVECs, and a 54% and 65% inhibition of TNF-alpha-induced IL-8 and MCP-1 secretion by physiological and physiologically high doses of 17beta-estradiol. The hormone did not affect the transcription of both chemokine genes. Tamoxifen reverted the inhibitory effect induced by 17beta-estradiol. In conclusion, 17beta-estradiol modifies the adhesion of leukocytes to endothelial cells by inhibiting the secretion, but not the gene transcription, of proinflammatory chemokines.
J Neuroendocrinol. 2002 Sep;14(9):731-6.
Lack of effect of testosterone and dihydrotestosterone compared to 17beta-oestradiol in 1-methyl-4-phenyl-1,2,3,6, tetrahydropyridine-mice.
Ekue A, Boulanger JF, Morissette M, Di Paolo T.
Molecular Endocrinology and Oncology Research Center, Laval University Medical Center, CHUL and Faculty of Pharmacy, Laval University, Quebec, Canada.
Previous work from our laboratory has demonstrated prevention of 1-methyl-4-phenyl-1,2,3,6, tetrahydropyridine (MPTP)-induced striatal dopamine depletion in C57Bl/6 mice by 17beta-oestradiol, progesterone and raloxifene. The activity of androgenic compounds in MPTP mice has received less attention and was the object of the present investigation. The effects of 17beta-oestradiol (2 microg/day), testosterone (100 microg/day) and dihydrotestosterone (DHT) (2 microg/day or 100 microg/day) were studied during 5 days before and after an acute treatment of four MPTP (10 mg/kg) injections in male C57Bl/6 mice. Striatal concentrations of dopamine and its metabolites dihydroxyphenylacetic acid and homovanillic acid were measured by high-performance liquid chromatography. MPTP mice treated with saline showed large decreases in dopamine and its metabolites compared to control mice. 17beta-oestradiol partially spared this decrease whereas testosterone and DHT did not. Striatal specific binding to the dopamine transporter (DAT) and to the vesicular monoamine transporter (VMAT2) were measured using [125I] RTI-121 and [3H] dihydrotetrabenazine autoradiography, respectively. As with striatal dopamine concentrations, MPTP treatment caused a decrease in DAT and VMAT2 specific binding. 17beta-oestradiol partially spared this decrease, whereas androgens did not. In the substantia nigra, DAT mRNA was measured by in situ hybridization. MPTP treatment induced a significant, but smaller decrease in substantia nigra DAT mRNA than striatal DAT protein. In addition, 17beta-oestradiol completely prevented the MPTP-induced decrease of DAT mRNA, whe
J Clin Endocrinol Metab. 2002 Sep;87(9):4341-9.
17Beta-estradiol up-regulates vascular endothelial growth factor receptor-2 expression in human myometrial microvascular endothelial cells: role of estrogen receptor-alpha and -beta.
Gargett CE, Zaitseva M, Bucak K, Chu S, Fuller PJ, Rogers PA.
Centre for Women's Health Research, Monash University Department of Obstetrics and Gynaecology, Monash Medical Centre, Clayton, Victoria 3168, Australia. caroline.gargeted.monash.edu.au
Estrogen has a cardiovascular protective role in women due in part to its effect on the vasculature. The roles of the two estrogen receptors (ERs), ERalpha and ERbeta, in the vascular actions of estrogen are unclear, as are effects of estrogen on microvascular endothelial cells (MEC) derived from sex steroid-responsive tissues. The present study demonstrates that 17beta-estradiol, but not progesterone, increases vascular endothelial growth factor (VEGF) receptor (VEGFR) expression on human myometrial MEC measured using biotin-recombinant human (rh) VEGF(165) and flow cytometry. This response occurred in a time- and dose-dependent manner, with significantly increased rhVEGF(165) binding at 3 h and maximal responses between 0.1 and 10 nmol/liter 17beta-estradiol, which was blocked by the antiestrogen ICI 182,780. Approximately 60% of samples demonstrated this response to 17beta-estradiol. All samples of myometrial MEC expressed both ERbeta mRNA and protein demonstrated by semiquantitative RT-PCR and Western blotting. However, ERalpha mRNA and protein were expressed in only 13 of 21 MEC samples. There was a significant association between ERalpha expression in myometrial MEC and their ability to respond to 17beta-estradiol by increasing rhVEGF(165) binding. 17beta-estradiol increased VEGFR-2 expression in ERalpha-expressing MEC isolates, which also demonstrated increased rhVEGF(165) binding, but failed to have these effects on ERalpha negative samples. Similarly, 17beta-estradiol augmented VEGF-induced MEC proliferation in ERalp
Surgery. 2002 Aug;132(2):302-9.
17-Beta-estradiol protects the liver against warm ischemia/reperfusion injury and is associated with increased serum nitric oxide and decreased tumor necrosis factor-alpha.
Eckhoff DE, Bilbao G, Frenette L, Thompson JA, Contreras JL.
Division of Transplantation, Department of Surgery, University of Alabama at Birmingham, 35294, USA.
BACKGROUND: Ischemia/reperfusion injury (I/R injury) to the liver can occur in low-flow states associated with trauma and shock and surgical procedures such as liver transplantation. Recent studies have shown that the administration of the female sex hormone 17-beta-estradiol after trauma-hemorrhage in animals restores depressed cardiac, hepatocellular, and immune functions. In this study we evaluated the effects of 17-beta-estradiol on I/R injury to the liver. METHODS: The medial lobe of the liver in normal male C57BL/6 mice was clamped at its base for 90 minutes. 17-Beta-estradiol was given 1 hour before I/R injury at 40 and 4000 microg/kg intraperitoneally. Biochemical analysis was performed, and liver biopsy specimens were obtained at 24 hours. RESULTS: A dose-dependent reduction in aspartate aminotransferase level was observed in animals (n = 8) given estradiol (243 +/- 23 IU/L) compared with saline-treated animals (902 +/- 42 IU/L, P <.001). The majority (90%) of the cytoprotective effect of estradiol was reverted by ICI 182,780 (a potent estrogen receptor antagonist). A significant increase in serum nitric oxide (NO) level was observed in animals given estradiol compared with controls; the effect was reversed by ICI 182,780 and N-nitro-L-arginine-methyl ester (an inhibitor of NO synthesis). A reduction in serum tumor necrosis factor-alpha was observed after injury in animals given estradiol compared with controls (30.2 +/- 11.1 vs 75.8 +/- 17.2 pg/mL, P <.001). Estradiol treatment significantly reduced liver necrosis, disintegration of hepatic cords, and neutrophil infiltration in an estrogen receptor-dependen
Am J Physiol Cell Physiol. 2003 Jul;285(1):C139-49. Epub 2003 Mar 26.
Mechanism for normal splenic T lymphocyte functions in proestrus females after trauma: enhanced local synthesis of 17beta-estradiol.
Samy TS, Zheng R, Matsutani T, Rue LW 3rd, Bland KI, Chaudry IH.
Department of Surgery, University of Alabama School of Medicine, Birmingham, AL 35294, USA.
Trauma-hemorrhage and resuscitation (TH) produces profound immunodepression and enhances susceptibility to sepsis in males but not in proestrus females, suggesting gender dimorphism in the immune responses. However, the mechanism responsible for the maintenance of immune functions in proestrus females after TH is unclear. Splenic T lymphocytes express receptors for estrogen (ER), contain enzymes involved in estrogen metabolism, and are the major source of cytokine production; the metabolism of 17beta-estradiol was assessed in the splenic T lymphocytes of proestrus and ovariectomized mice by using appropriate substrates after TH. Analysis for aromatase and 17beta-hydroxysteroid dehydrogenases indicated increased 17beta-estradiol synthesis and low conversion into estrone in T lymphocytes of proestrus but not of ovariectomized mice. The effect of 17beta-estradiol on T lymphocyte cytokine release was reliant on ER expressions. This was apparent in the differences of ER expression, especially that of ER-beta, and an association between increased 17beta-estradiol synthesis and sustained release of IL-2 and IL-6 in T lymphocytes of proestrus females after TH. Because 17beta-estradiol is able to regulate cytokine genes, and the splenic T lymphocyte cytokine releases is altered after TH, continued synthesis of 17beta-estradiol in proestrus females appears to be responsible for the maintenance of T lymphocyte cytokine release associated with the protection of immune functions after TH.
FEBS Lett. 2002 Sep 11;527(1-3):63-6.
Estradiol receptor potentiates, in vitro, the activity of 5-methylcytosine DNA glycosylase.
Jost JP, Thiry S, Siegmann M.
Friedrich Miescher Institute, Maulbeerstrasse 66, CH-4058, Basel, Switzerland. josmi.ch
At a concentration of 5 x 10(-9) M of hemi-methylated DNA (one order of magnitude below the K(m)), MCF-7 (a human breast carcinoma cell line) nuclear extracts potentiate the activity of 5-methylcytosine DNA glycosylase (5-MCDG, alias G/T mismatch DNA glycosylase). Depending on the ratio between MCF-7 nuclear extracts and 5-MCDG, there is an up to 10-fold increase in 5-MCDG activity. The potentiation of 5-MCDG by MCF-7 nuclear extracts requires an estradiol response element adjacent to the hemi-methylated site. Depletion of the estradiol receptor from MCF-7 nuclear extracts with specific antibodies abolishes the potentiation of 5-MCDG activity. The estradiol receptor present in MCF-7 nuclear extracts can be precipitated with antibodies directed against 5-MCDG. Reciprocally, antibodies directed against the estradiol receptor precipitate 5-MCDG. The results indicate the formation of a complex between the estradiol receptor and 5-MCDG.
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