Effects of 17-beta estradiol and tamoxifen in chronic ocular hypertension mouse model / 国际眼科杂志(Guoji Yanke Zazhi)

· AIM:To explore the modulation effects of 17-β estradiol (E2) and tamoxifen (TAM) in chronic intraocular hypertension mouse model.· METHODS:We performed anterior chamber injection of magnetic beads to induced chronic ocular hypertension models.Adult C57BL/6 male mice were used in the experiments and randomly divided into four groups:control,Beads group,E2 group and E2+TAM group.The intraocular pressure (lOP) were measured by Tonolab tonometer.Central retinal thickness was evaluated by HE staining.Brn3a as a specific marker of retinal ganglion cells (RGCs),were stained and counted by immunohistochemistry (IHC) staining.Glial fibrillary acidic protein (GFAP) as a marker of proliferation of astrocytes,was quantified using western blotting.· RESULTS:The IOP level was significantly elevated after anterior chamber injection of magnetic beads compared to control group (P＜0.05),while in E2 and E2+TAM group,the IOP levels were reduced (P＜ 0.05 vs Beads group),especially in E2+TAM group in 2wk.The RGCs happened to degenerated in Beads group after 2wk,while the effects were reversed by E2+TAM (P＜0.05).The central retinal thickness showed no significant statistical difference among the four groups after 2wk (P ＞ 0.05).The expression level of GFAP increased caused via beads injection,however,decreased in E2 and E2+TAM group (P＜0.05).· CONCLUSION:E2 and E2+TAM could both effectively decrease the IOP level in chronic intraocular hypertension mouse model,increase the survival of RGCs from high intraocular pressure,suppress expression of GFAP,which indicated neuroprotective effects of E2 and TAM in glaucoma through an anti-inflammatory effects.

17Beta-estradiol Stimulates Glucose Uptake Through Estrogen Receptor and AMP-activated Protein Kinase Activation in C2C12 Myotubes

BACKGROUND: Previous studies have shown that 17beta-estradiol activates AMP-activated protein kinase (AMPK) in rodent muscle and C2C12 myotubes and that acute 17beta-estradiol treatment rapidly increases AMPK phosphorylation possibly through non-genomic effects but does not stimulate glucose uptake. Here, we investigated whether 24-hour 17beta-estradiol treatment stimulated glucose uptake and regulated the expression of genes associated with glucose and energy metabolism through the genomic effects of estrogen receptor (ER) in C2C12 myotubes. METHODS: C2C12 myotubes were treated with 17beta-estradiol for 24 hours, and activation of AMPK, uptake of glucose, and expression of genes encoding peroxisome proliferator-activated receptor γ coactivator 1α, carnitine palmitoyltransferase 1β, uncoupling protein 2, and glucose transporter 4 were examined. Furthermore, we investigated whether AMPK inhibitor (compound C) or estrogen receptor antagonist (ICI182.780) treatment reversed 17beta-estradiol-induced changes. RESULTS: We found that 24-hour treatment of C2C12 myotubes with 17beta-estradiol stimulated AMPK activation and glucose uptake and regulated the expression of genes associated with glucose and energy metabolism. Treatment of C2C12 myotubes with the estrogen receptor antagonist (ICI182.780) reversed 17beta-estradiol-induced AMPK activation, glucose uptake, and changes in the expression of target genes. Furthermore, treatment with the AMPK inhibitor (compound C) reversed 17beta-estradiol-induced glucose uptake and changes in the expression of target genes. CONCLUSION: Our results suggest that 17beta-estradiol stimulates AMPK activation and glucose uptake and regulates the expression of genes associated with glucose and energy metabolism in C2C12 myotubes through the genomic effects of ER.

Effects of 17 β-estradiol and 2-methoxyestradiol on Endothelin-1/Nitric Oxide Cascade in Experimental Rats With Hypoxic Pulmonary Hypertension / 中国循环杂志

Objective: To explore the effects of 17 β-estradiol (E2) and 2-methoxyestradiol (2ME) on endothelium-1/nitric oxide (ET-1/NO) cascade in experimental rats with hypoxic pulmonary hypertension. Methods: A total of 48 female SD rats were randomly divided into 6 groups:①Sham operation group,②Ovariectomy (OVX) group,③Hypoxia group,④OVX+hypoxia group,⑤OVX+hypoxia+E2 group, the rats received subcutaneous E2 at 20μg/(kg?d) and⑥OVX+hypoxia+2ME group, the rats received subcutaneous 2ME at 240μg/(kg?d).n=8 in each group. Blood levels of ET-1, NO, eNOS activity and the expressions of pulmonary tissue endothelium A receptor (ETAR), ETBR and eNOS were compared among different groups. Results: Compared with Sham operation group, Hypoxia and OVX+hypoxia groups showed small pulmonary artery thickening with lumen narrowing, increased mean pulmonary arterial pressure (mPAP), allP<0.01; the above morphological and mPAP changes were reduced by E2 and 2ME intervention. Compared with Sham operation group, OVX and Hypoxia groups had increased blood ET-1 and pulmonary mRNA, protein expressions of ETAR, decreased pulmonary ETBR, all P<0.01; the above changes were more obvious in OVX+hypoxia group; E2 and 2ME intervention reduced blood ET-1 and pulmonary ETAR expression, but they were still higher than Sham operation group, meanwhile, ETBR expression was elevated, but it was still lower than Sham operation group, allP<0.01; blood ET-1 was lower in OVX+hypoxia+2ME group than OVX+hypoxia+E2 group,P<0.05. Compared with Sham operation group, OVX group had decreased pulmonary eNOS protein expression,P<0.01; Hypoxia group had decreased blood NO and pulmonary eNOS protein expression,P<0.05 orP<0.01; OVX+hypoxia group had decreased blood NO, eNOS activity and decreased pulmonary mRNA and protein expressions of eNOS, allP<0.01; E2 and 2ME intervention elevated the above indexes,P<0.05 orP<0.01, but they were still lower than Sham operation group, allP<0.05. Conclusion: E2 and 2ME could decrease blood ET-1 and pulmonary ETAR expression, increase pulmonary ETBR expression; elevate blood NO, eNOS activity and pulmonary eNOS expression. E2 and 2ME may partially reverse pulmonary hypertension via improving ET-1/NO cascade in experimental rats.

Differential regulation of senescence and in vitro differentiation by 17β-estradiol between mesenchymal stem cells derived from male and female mini-pigs

The characterization and potential of mesenchymal stem cells (MSCs) are gender dependent and estrogen influences these properties. This study demonstrated that supplementation with 17β-estradiol (E2) increases the proliferation of bone marrow-MSCs derived from male and female mini-pigs (Mp- and Fp-BMSCs) in a concentration-dependent manner, with 10(-12) M E2 suggested as the optimal dose of E2 that led to the greatest improvement in BMSCs proliferation. Supplementation of 10(-12) M E2 resulted in down-regulation of β-galactosidase activity and pro-apoptotic activity in both BMSCs, while anti-apoptotic activity was up-regulated in only Fp-BMSCs. Further, E2 increased the osteogenic ability of Fp-BMSCs. Based on these findings, optimal utilization of E2 can improve cellular senescence and apoptosis, as well as in vitro osteogenesis of BMSCs, and could therefore be useful in stem cell therapy, particularly in bone regeneration for adult females.

Fermented soybeans by Rhizopus oligosporus reduce femoral bone loss in ovariectomized rats

BACKGROUND/OBJECTIVES: Soy isoflavones are structurally similar to estrogen and bind to estrogen receptors, suggesting that they exhibit estrogenic activities; therefore, they are referred to as phytoestrogens. Fermentation may affect the bioavailability of isoflavones altering soy isoflavone glycosides in the form of aglycones. Thus, this study investigated the effects of fermented soybeans by Rhizopus oligosporus on bone metabolism in both young rats as a pilot test and in ovariectomized (ovx) old rats as a model of menopause. MATERIALS/METHODS: In the pilot test, a total of 24 seven-week-old female Sprague-Dawley (SD) rats were fed one of three diets for a period of four weeks: casein, unfermented soybean product, or fermented soybean product by R. oligosporus. In the ovx rat model, 20-week-old SD rats weighing 260-290 g underwent either sham-operation (n = 10) or bilateral ovariectomy (n = 30) and were then fed the AIN-93M diet for one week. Thereafter, rats were fed sham-casein, ovx-casein, ovx-soybean, or ovx-fermented soybean diet for five weeks. After decapitation, femoral bones were isolated and preserved in 9% formalin for assessment of bone mineral density (BMD), bone mineral content (BMC), and bone-breaking strength (BBS). RESULTS: Ovx rats showed significantly increased weight gain and decreased uterine wet weight. Of particular interest, ovx rats fed fermented soybeans showed increased uterine wet weights compared to control rats. Fermented soybean diet caused a significant increase in plasma 17-beta estradiol concentrations in young rats, and 17-beta estradiol levels were enhanced in ovx rats to match those of sham-operated ones. Significantly lower femoral BMD and BMC were observed in ovx rats compared to sham-operated controls, whereas bone areas did not differ statistically among the groups. In addition, BBS tended to be increased in ovx rats fed soybeans and fermented soybeans. CONCLUSIONS: Supplementation of fermented soybeans could have preventive and therapeutic effects against osteoporosis in postmenopausal women.

Osteogenic Response of Human Osteoblasts Derived from Mandible and Maxilla: A Preliminary Study

17beta-estradiol Attenuates Renal Fibrosis in Mice with Obstructive Uropathy

PURPOSE: Men are generally more prone to chronic renal disease and progression to end stage renal disease than women. The purpose of this study is to prove the effect of gender and sex hormone on renal fibrosis in mice with unilateral ureteral obstruction (UUO) and to elucidate the specific underlying mechanisms. METHODS: We compared the expression of alpha-smooth muscle actin (alpha-SMA) in female and male mice with complete UUO (day 7). After this, we estimated the changes of renal fibrosis in the female mice with oophorectomy and in the female mice with oophorectomy and replacement of 17beta-estradiol, respectively. RESULTS: The level of alpha-SMA in the female kidney with UUO was significantly lower than that in the male kidney with UUO. oophorectomy and replacement of 17beta-estradiol did not change the expression of angiotensin II type 1 (AT1) receptor in the female kidney with UUO, whereas the expression of angiotensin II type 2 (AT2) receptor was significantly more elevated in the intact female (IF) and the oophorectomized female with estrogen (OF+E) than that in the oophorectomized female (OF). The expressions of inducible nitric oxide synthase (iNOS) in the IF and OF+E mice were significantly more elevated than that in the OF mice, which was similar to the expression of AT2 receptor. CONCLUSION: The female gender is associated with resistance to renal fibrosis in obstructive uropathy and this gender difference may originate from the existence of 17beta-estradiol, which has an anti-fibrotic effect via upregulation of the AT2 receptor and iNOS.

Effects of Sigma Anti-bonding Molecule Calcium Carbonate on bone turnover and calcium balance in ovariectomized rats / 한국실험동물학회지

This study was conducted to evaluate the effect of Sigma Anti-bonding Molecule Calcium Carbonate (SAC) as therapy for ovariectomy-induced osteoporosis in rats. Three weeks after surgery, fifteen ovariectomized Sprague-Dawley rats were divided randomly into 3 groups: sham-operated group (sham), ovariectomized group (OVX) and SAC-treatment group (OVX+SAC). The OVX+SAC group was given drinking water containing 0.0012% SAC for 12 weeks. Bone breaking force and mineralization as well as blood parameters related to the bone metabolism were analyzed. In OVX animals, blood concentration of 17beta-estradiol decreased significantly, while osteocalcin and type I collagen C-terminal telopeptides (CTx) increased. Breaking force, bone mineral density (BMD), calcium and phosphorus in femurs, as well as uterine and vaginal weights, decreased significantly following OVX. However, SAC treatment (0.0012% in drinking water) not only remarkably restored the decreased 17beta-estradiol and increased osteocalcin and CTx concentrations, but also recovered decreased femoral breaking force, BMD, calcium and phosphorus, although it did not reversed reproductive organ weights. It is suggested that SAC effectively improve bone density by preventing bone turnover mediated osteocalcin, CTx and minerals, and that it could be a potential candidate for therapy or prevention of postmenopausal osteoporosis.

Effects of Drospirenone (2 mg) with 17beta-estradiol (1 mg) on Blood Pressure, Body Weight, and Lipid Profiles in Postmenopausal Korean Woman / 대한폐경학회지

OBJECTIVES: The objective of the present study was to determine the effects of the widely used combination hormone therapy, drospirenone and 17beta-estradiol on the blood pressure, body weight, lipid profiles, and major side effects in postmenopausal Korean women. METHODS: Four hundred seventeen menopausal patients who were being treated with drospirenone/17beta-estradiol at the Asan Medical Center between December 2007 and October 2010 underwent a retrospective chart review. One hundred twenty-five patients were divided into 2 groups based on blood pressure, as follows: group 1 (normal blood pressure, n = 76); and group 2 (stage 1 hypertension and pre-hypertension, n = 49). The systolic and diastolic blood pressure and the body weight were checked before the treatment, and 1, 2, 3, 6, 9, 12, 18 and 24 months after taking the medication. RESULTS: The median days of administration were 279. The combination of drospirenone and 17beta-estradiol had a blood pressure-lowering effect in groups 1 and 2. However, the body weight did not show a statistically significant change. Only the level of triglycerides decreased with time and the change was statistically significant. The low density lipoprotein (LDL)-cholesterol and triglycerides levels had a statistically significant decrease 18 months after the medication. The most common reasons for discontinuouing medication were vaginal spotting (28%), fear of side effects (27%), and ineffectiveness (26%). CONCLUSION: The combination of drospirenone/17beta-estradiol caused a decrease in systolic and diastolic blood pressure and the body weight showed no statistically significant decrease. Furthermore, triglycerides showed statistically significant decrease and there were no severe side effects of the medication reported.

Role of extracellular signal-regulated protein kinase in estrogen-induced proliferation of breast cancer cell line MCF-7 / 第二军医大学学报

Objective: To investigate the role of extracellular signal-regulated protein kinase (ERK) in estrogen-induced proliferation and cell cycle transformation of breast cancer cell line MCF-7 and the related mechanisms. Methods: Estrogen receptor-positive breast cancer cell line MCF-7 was used in our study. The effects of 17β-E2 on the proliferation of MCF-7 cells was investigated by MTT assay to determine the optimal concentration of 17β-E2 for the following experiment. The effect of PD98059 on 17β-E2-induced proliferation of MCF-7 cells was measured by MTT assay to determine the intermediate concentration of PD98059. The cell cycle was analyzed by flow cytometry and telomerase activity was determined by Telomerase repeat amplification protocol PCR (TRAP-PCR) silver staining. The expression of wild-type p53 and phosphorylated ERK1/2 protein was determined by Western blotting and the expression of wild-type p53 mRNA was detected by RT-PCR. Results: ERK phosphorylation inhibitor PD98059 inhibited the proliferation of MCF-7 cells treated with 17β-E2 in a time- and dose-dependent manner(P<0.01). The intermediate concentrations of PD98059 were 89.28 μmol/L for 24 h, 39.81 μmol/L for 48 h and 21.87 μmol/L for 72 h. Treatment with 20 μmol/L PD98059 for 48 h reversed the promoting effect of 17β-estradiol on the cell cycle transformation of MCF-7, increasing the number of G1 phase cells and decreasing the number of S and M phase cells (P<0.01), inhibited the enhancing effect of 17β-E2 on the telomerase activity of MCF-7 cells(P<0.05), increased the protein expression level and genetic transcription of wild-type p53 (P<0.01), and decreased the expression of p-ERK1/2 protein(P <0.01). Conclusion: ERK plays an important role in 17β-E2-induced proliferation and cell cycle transformation of breast cancer cell line MCF-7, which might be related to the changes of genetic transcription of wild type p53 and telomerase activity.

Gene Expression Profiles of Uterine Normal Myometrium and Leiomyoma and Their Estrogen Responsiveness In Vitro

BACKGROUND: Uterine leiomyomas are common benign smooth muscle tumors among the reproductive aged-women. The research has been aimed to identify the differentially expressed genes between normal myometrium and leiomyoma and to investigate the effects of E2 on their expression. METHODS: Gene microarray analysis was performed to identify the differentially expressed genes between normal myomerium and leiomyoma. The data was confirmed at protein level by tissue microarray. RESULTS: Gene microarray analysis revealed 792 upregulated genes in leiomyoma. Four genes (tropomyosin 4 [TPM4], collagen, type IV, alpha 2 [COL4alpha2], insulin-like growth factor binding protein 5 [IGFBP5], tripartite motif-containing 28 [TRIM28]) showed the most dramatic upregulation in all leiomyoma samples. Tissue microarray analyses of 262 sample pairs showed significantly elevated expression of TPM4, IGFBP5, estrogen receptor-alpha, and progesterone receptor (PR) protein in leiomyoma from the patients in their forties, COL4alpha2 in the forties and fifties age-groups, and TRIM28 in the thirties age-group. PR, insulin-like growth factor 1 (IGF-1), IGF-1 receptor (IGF-1R) and IGFBP5 were induced by E2 in in vitro culture of tissue explants from which cells migrated throughout the plate. Among these, PR, IGF-1, IGFBP5 genes showed higher expression in tissue compared to cells-derived from tissue in leiomyoma and IGF-1R in leiomyoma cell. CONCLUSIONS: This observation implies the importance of the whole tissue context including the cells-derived from tissue in the research for the understanding of molecular mechanism of leiomyoma. Here, we report higher expression of TRIM28 in leiomyoma for the first time and identify E2-responsive genes that may have important roles in leiomyoma development.

Reactive Oxygen Species Generated by 17beta-estradiol Play a Role in the Up-regulation of GPX4 Protein in MCF-7 Breast Cancer Cells / 한국유방암학회지

PURPOSE: Estrogen is known to act as both a growth factor and a survival factor for breast cancer. The responsible molecular mechanisms remain, however, to be fully elucidated. We hypothesize that the effect of estrogen relates to its ability to induce the cellular antioxidant defense enzymes. METHODS: In the presence study, we examined the ability of 17beta-estradiol (E2) to regulate the level of phospholipid hydroperoxide glutathione peroxidase (GPX4) protein, which is an anti-oxidative enzyme that can directly reduce both phospholipids and cholesterol-hydroperoxides located in the cell membranes and lipoproteins. RESULTS: E2 elicited a dose- and time-dependent increase in the GPX4 expression in the MCF-7 breast cancer cells, and this up-regulation was blocked by the free radical scavenger N-acetylcysteine (NAC). Additionally, we confirmed that E2 triggered a rapid and transient increase in the intracellular reactive oxygen species (ROS) levels, and this E2-induced increase in the ROS levels was inhibited by pretreatment with NAC. Moreover, such ROS inducers as TGF-beta, TNF-alpha and insulin induced an increase in the level of GPX4 protein. However, estrogen receptor (ER)alpha knockdown by transfection with ERalpha-siRNA did not significantly change the GPX4 protein level that was induced by E2. Furthermore, pre-incubation with the ER antagonist ICI 182,780 did not inhibit E2-mediated GPX4 induction. Conversely, pretreatment of cells with LY294002, a pharmacological inhibitor of phosphatidylinositol 3-kinase inhibitor, suppressed the E2-augmented GPX4 expression. CONCLUSION: Collectively, our data show that E2 may partly provide a survival advantage through the regulation of cellular oxidative homeostasis in MCF-7 breast cancer cells.

Parasitic castration, growth, and sex steroids in the freshwater bonefish Cyphocharax gilbert (Curimatidae) infested by Riggia paranensis (Cymothoidea)

Cyphocharax gilbert shows parasitic castration when infested by the crustacean Riggia paranensis, being unable to reproduce. Fish were sampled in the middle rio Itabapoana, Brazil, to study the prevalence of parasitism, growth, and sex steroid concentrations, considering the body size, sex, and reproductive condition of specimens. Most of the fish analyzed were infested (56.0 percent). The presence of two lines on the scales was more frequent among infested fish (22.0 percent) than among fish without parasites (12.0 percent for females and 10.0 percent for males). The occurrence of three lines on the scales was rare (3.5 percent among infested and 2.0 percent among females without parasites). These results suggest that growth of the host is faster than that of non infested fish. The serum concentrations of sex steroids from fish without parasites varied at different gonadal development stages (17 beta-estradiol: 60.0 to 976.7 pg/ml; total testosterone: 220.0 to 3,887.7 pg/ml). All infested fish had lower levels of the two sex steroids and undeveloped gonads. Sex steroids levels in infested females were close to those in females at post-spawning stages. Total testosterone concentrations of infested males were below those of males at early gonadal maturation stage. These results suggest that R. paranensis reduces the reproductive capacity of C. gilbert by affecting the host endocrine system

Cyphocharax gilbert exibe castração parasitária quando está infestado pelo crustáceo Riggia paranensis, estando impossibilitado de reproduzir. Os peixes foram coletados no trecho médio do rio Itabapoana, Brasil, para analisar a prevalência do parasitismo, quantificar crescimento e as concentrações de esteróides sexuais, considerando o tamanho do corpo, o sexo e a condição reprodutiva dos espécimes. A maioria dos peixes analisados estava infestada (56,0 por cento). A presença de duas linhas em escamas foi mais freqüente entre os peixes infestados (22,0 por cento) que entre os peixes não infestados (12,0 por cento para as fêmeas e 10,0 por cento para os machos). A presença de três linhas na escama foi rara (3,5 por cento entre os peixes infestados e 2,0 por cento entre as fêmeas não infestadas). Estes resultados sugerem que o crescimento no hospeideiro pode ser mais rapido que no peixes não parasitados. As concentrações de esteróides sexuais no soro dos peixes não infestados variaram entre os diferentes estágios reprodutivos (17 beta-estradiol: 60,0 a 976,7 pg/ml; total testosterona: 220,0 a 3.887,7 pg/ml). Todos os peixes infestados apresentaram baixos níveis dos dois hormônios esteroidais e ausência de desenvolvimento gonadal. Os níveis de esteróides sexuais nas fêmeas infestadas foram próximos aos níveis encontrados nas fêmeas pós-desovadas. A concentração de testosterona encontrada nos machos infestados foi inferior àquela obtida nos machos que estavam iniciando o desenvolvimento gonadal. Estes resultados sugerem que R. paranensis impede a reprodução de C. gilbert, afetando o sistema endócrino do hospedeiro

Up-regulation of P13K/Akt Signaling by 17 beta-estradiol through Activation of Estrogen Receptor-alpha in Breast Cancer Cells / 한국유방암학회지

PURPOSE: Estrogen stimulates cell proliferation in breast cancer, the biological effects of which are mediated through two intracellular receptors: estrogen receptor-alpha (ERalpha) and estrogen receptor-beta (ERbeta). However, the actual role of ERs in the proliferative action of estrogen remains to be established. It was recently found that ER activates phosphatidylinositol-3-OH kinase (PI3K), via its binding with the p85 regulatory subunit of PI3K. Therefore, possible mechanisms may include ER-mediated phosphoinositide metabolism, with the subsequent formation of phosphatidylinositol-3, 4, 5-trisphosphate (PIP(3)), which is generated from phosphatidylinositol 4, 5-bisphosphate (PIP(2)) via PI3K activation. The present study has demonstrated that 17b-estradiol (E2) up-regulates PI3K in an ERalpha, but not an ERbeta dependent manner, and also stimulates cell growth in breast cancer cells. METHODS: To study this phenomenon, we treated ER-positive MCF-7 cells and ER-negative MDA-MB-231 cells with 10 nM E2. RESULTS: The treatment of MCF-7 cells with E2 resulted in a marked increase in the expression of PI3K (p85), which was paralleled by increases in the levels of phospho-Akt (Ser-473) and PIP3. These observations were also correlated with increased E2-induced cell proliferation activity. However, no effects of E2 on breast cancer cells were observed in the MDA-MB-231 cell line, indicating the pathway of E2-mediated up-regulation of PI3K/Akt is ERalpha-dependent. CONCLUSION: These results suggest that estrogen activates PI3K/Akt signaling via an ERalpha-dependent mechanism in MCF-7 cells.

A influência da soja orgânica e transgênica nos indicadores bioquímicos de doenças cardiovasculares em ratos / The influence of organic and transgenic soy in biochemical indicators of cardiovascular disease in rats

A soja é um alimento rico em proteínas, fibras vitaminas minerais e isoflavonas. A soja orgânica é cultivada livre de produtos químicos. O tipo transgênico foi criado para aumentar a produção e reduzir custos, porém há muitas dúvidas sobre seus efeitos no homem e no meio ambiente...O presente estudo mostrou que as dietas experimentais não tiveram bom desempenho na infância, mas ma idade adulta e velhice, apresentaram aproveitamento semelhante à proteína de origem animal. O uso da soja orgânica e transgênica pareceu reduzir os níveis de colesterol e triglicerídeos, mas também diminuiu os níveis de 17 beta estradiol que pode não ser considerado benéfico, principalmente na menopausa onde seus níveis diminuem naturalmente.

The Effects Of 17 beta-Estradiol On Osseous Tissue In Ovariectomized Rats

Protective effect of 17beta-Estradiol Against Reperfusion Arrhythmias in Cats

BACKGROUND: Although reperfusion certainly prevents tissue ischemia from possible cardiac death, several lines of evidence suggest that reperfusion may paradoxically aggravate the frequency of serious reperfusion-induced lethal arrhythmias. It has been reported that acute administration of estrogen at physiological concentrations reduced with myocardial ischemic injury in women with coronary heart disease. In studies with canines, acute administration by either the intra-muscular or the intra-coronary route similarly prevented ischemia and reperfusion dysrhythmias and also reduced the infarct size because the estrogen increased the distal coronary perfusion pressure, scavenged free radicals and had other effects during both ischemia and reperfusion. However, the canine heart is notoriously well collateralized. 17beta-estradiol induces very little vasorelaxation in cat coronary rings, suggesting that increased ischemic myocardial blood flow dose not contribute to the protective effect. In the present study, employing a cat model of regional cardiac ischemia, we examined whether reperfusion rendered after acute administration of 17beta-estradiol could lower the incidence of reperfusion-induced lethal arrhythmia and the death rate. METHOD: Adult mongrel male cats(n=31, 2.7~4.5 kg) were anesthetized under positive-pressure artificial ventilation with room air. Electrocardiograms were recorded. The animals of the control group(n=15) were subjected to 20-minute left anterior descending coronary artery(LAD) occlusion followed by abrupt reperfusion. The animals in the experimental 17beta-estradiol(2 or 20 microgram/kg) group were subjected to ischemia/reperfusion insult following drug treatment: 17beta-estradiol was applied intravenously within the 60 seconds just before LAD ligation followed by abrupt reperfusion. The Fisher's exact test was used to compare the data from different animal groups(p<0.05). RESULTS: The number of arrhythmias(ventricular premature beat, ventricular tachycardia and ventricular fibrillation) emerging during the reperfusion phase were not statistically different from that in the control group. The death rate in the 17beta-estradiol 20 microgram/kg group was lower from that in the control group(P value = 0.039). CONCLUSION: Acute administration of 17beta-estradiol at a supraphysiological concentration might produce cardioprotective effects, not by modificating the coronary blood flow into the threatened myocardial region, but by other mechanisms that directly or indirectly increase the intrinsic myocardial ischemic tolerance in the cat during the reperfusion phase.

Change in the Gene Expression of HOS Cell Line by 17beta-Estradiol -Study using cDNA Array- / 대한정형외과연구학회지

Osteoporosis is caused by the decrease in bone mass associated with disturbance in bone remodeling. Bone remodeling depends on the spatial and temporal coupling of bone formation by osteoblasts and bone resorption by osteoclasts. However, the molecular basis of these inductive interactions is unknown. To establish a new way of study on the function of osteoblast, the profile of genes expressed in proliferating osteoblast cell line was investigated using cDNA array of 588 genes. Among 232 genes expressed in HOS cell line, the most abundantly expressed gene was 40S ribosomal protein S19. The glutathione S-transferase pi gene and thymosin beta-10 gene were expressed highly also. The expressed genes were 23 oncogenes and tumor suppressors, genes for 20 cell cycle control proteins, 1 ion channels, 30 modulators/effectors/intracellular transducers, 6 stress response proteins, 24 apoptosis-related protein, 16 DNA synthesis/DNA repair/recombination proteins, 36 DNA binding/transcription factors, 35 cell receptorsl, and 41 extracellular cell signalling and communication proteins. The expressions of ten genes were changed by treatment of 17beta-estradiol. Eight genes were overexpressed and two genes were down-regulated by 17beta-estradiol. These results show the expression profile of genes in proliferating osteoblast cell line and show ten genes regulated by 17beta-estradiol.

Effect of estrogen on growth hormone receptor expression of human periodontal ligament cell line / 대한치과교정학회지

The present studies were performed to investigate the interaction of 17beta-estradiol and human growth hormone(hGH) on the proliferation of human periodontal ligament(hPDL) cell. The independent effects of 17beta-estradiol and hGH on hPDL cell proliferation were investigated and the effects of hGH on hPDL cell proliferation after 17beta-estradiol pre-treatment were also investigated. Lastly, the change of hGH receptor expression in hPDL cell after 17beta-estradiol pre-treatment were investigated The obtained results were as follows; 1. The treatment of 17beta-estradiol or hGH had no significant effects on hPDL cell proliferation. 2. After pre-treatment of 17beta-estradiol, hGH stimulated the proliferation of the hPDL cell, regardless of hHG concentration. 3. Although there was not hGH receptor in the hPDL cell, hGH receptors were expressed in hPDL cell after more than 6 hours pre-treatment cf 17beta-estradiol. 4. The effect of hGH on hPDL, cell proliferation was related to the hGH receptor expression. 17beta-estradiol pre-treatment contributed to the hGH effects on the hPDL cell by stimulating hGHR expression.

Effect of 17beta-Estradiol and 1,25-Dihydroxyvitamin D3 on Interleukin-6 Production of Periodontal Ligament Cells / 대한치주과학회지

Interleukin-6(IL-6) stimulate osteoclast differentiation. 17beta-estradiol, 1,25-dihydroxyvitamin D3(1,25-(OH)2D3) and interleukin-1beta inhibit or stimulate osteoclast differentiation by decreasing or increasing the synthesis of interleukin-6(IL-6) from stromal/osteoblastic cells, respectively. Periodontal ligament(PDL) cells reside between the alveolar bone and the cementum and have osteoblastic characteristics. To estimate the effect of 17beta-estradiol and 1,25(OH)2D3 on IL-6 production of PDL cells, PDL cells were treated with 17beta-estradiol or 1,25-(OH)2D3 in the absence or the presence of IL-1beta. The concentration of IL-6 produced form PDL cells was determined by enzym linked immunosorbent assay(ELISA). In unstimulated PDL cells, we detected constitutive production of IL-6 at 1st and 2nd day. IL-1beta increased IL-6 synthesis at 1st day and 2nd day. 17beta-estradiol had no significant effect on the secretion of this cytokine, either constitutively or after stimulation with IL-1beta(0.05 ng/ml). 1,25-(OH)2D3(10(-8)M) decreased not only constitutive IL-6 production but also IL-1beta-induced IL-6 production at 2nd day. These results suggest that 1,25-(OH)2D3 may control IL-1beta-induced osteoclast differentiation by decreasing IL-1beta-induced IL-6 secretion of PDL cells.