Simultaneous Determination of Main Components in Estrogenic Hormone Drug Nilestriol Tablets and Diethylstilbestrol Tablets by HPLC / 中国药房

OBJECTIVE： To establish the method for simultaneous determination of main drug contents in Nilestriol tablet and  Diethylstilbestrol tablet. METHODS： HPLC method was adopted. The determination was performed on Waters Symmetry C18 column with mobile phase consisted of 0.02 mol/L ammonium acetate water solution-acetonitrile （40 ∶ 60，V/V） at a flow rate of 1.0 mL/min. The detection wavelength was set at 280 nm， and column temperature was 35 ℃. The sample size was 20 μL. RESULTS： The linear range of nilestriol and diethylstilbestrol were 0.01-0.5 mg/mL （r＝0.999 9）； the limits of quantitation were 187 and 192 ng/mL， and the limits of detection were 56 and 58 ng/mL. RSDs of precision， stability and reproducibility tests were all lower than 1％ （n＝6）. The recoveries of them were 99.13％-100.80％（RSD＝0.52％，n＝9） and 99.20％-100.90％（RSD＝0.58％， n＝9）. CONCLUSIONS： The method is more sensitive and reproducible， and suitable for simultaneous determination of nilestriol content in estrogenic hormone drug Nilestriol tablets and diethylstilbestrol content in Diethylstilbestrol tablets.  

Impacts of DES on the expressions of related genes in the gubernaculums testis of newborn mice / 中华男科学杂志

Objective@#To investigate the influence of diethylstilbestrol (DES) on the mRNA expressions of the androgen receptor (AR), estrogen receptor α (ERα), proliferating cell nuclear antigen (PCNA), and actin alpha 1 (ACTα1) in the gubernaculums testis of newborn mice and explore their action mechanisms.@*METHODS@#A total of 140 male Kunming mice were randomly divided into a blank control, a dimethyl sulfoxide (DMSO) control, and 5 experimental groups to be treated subcutaneously with normal saline, DMSO, and DES at 0.02, 0.1, 0.5, 10 and 50 μg per kg of the body weight per day, respectively, at gestation days 9－17. On the first day after birth, the animals were sacrificed and the gubernaculums testis collected for detection of the mRNA expressions of AR, ERα, PCNA and ACTα1 by RT-PCR.@*RESULTS@#Compared with the DMSO control, the experimental groups, particularly the DES 10 and 50 μg groups, showed significant increases in the mRNA expression of ERα (RE2 = 0.825, P <0.05), but remarkable decreases in those of AR, PCNA and ACTα1 (RA2 = 0.713, RP2 = 0.946, RT2 = 0.960, P <0.01), all in a dose-dependent manner.@*CONCLUSIONS@#The AR, ERα, PCNA, and ACTα1 mRNA are expressed in the gubernaculum testis of normal newborn mice, and their expression levels may be influenced by intervention with different concentrations of DES during the gestation. Exogenous estrogens may affect the proliferation and contraction of gubernaculum testis cells and consequently the normal development of the testis or even the whole male reproductive system by influencing the metabolism of ER and/or AR.

Protective effect of red yeast rice capsule containing coenzyme Q10 on osteoporosis in rats induced by ovariectomy combined with D-galactose / 中国药理学通报

Aim To investigate the effects of red yeast rice capsules containing coenzyme Q10 on femur with an animal model of osteoporosis, which was induced by OVX with D-galactose in rats, and the results were compared with those obtained from diethylstilbestrol. Methods Three-month old female Sprague-Dawley rats were randomly divided into sham group ( CON ) , ovariectomized group ( OVX ) , model group ( MOD ) , diethylstilbestrol group( DES) , and red yeast rice cap-sule group( RYR) . After 60 days, the left femurs were collected for Ca, P and hyp measurement, while the right femurs were performed with three-point bending test and micro-CT evaluation, respectively. Results Compared with CON group, MOD group had a signifi-cant increase in body weight, Tb. Sp, SMI and signifi-cant decrease in maximum load, stiffness, maximum strength, break strength, elastic modulus, Ca, P, Hyp contents and indicators of BV/TV, Tb. N, BMD, Conn-Dens. On the other hand, compared with MOD group, RYR group had a lower body weight and all bone biomechanics indexes were increased without sta-tistically significant difference. At the same time, the content of Ca, P and indicators of BV/TV, Tb. N, Tb. Th, BMD, Conn-Dens increased significantly;yet Tb. Sp decreased significantly. In DES group, the results of indicators were consistent with those for RYR group. In addition, compared with DES group, in RYR group body weight decreased significantly;the content of Ca, P and indicators of BV/TV, Tb. N, Tb. Th, Conn-Dens were significantly higher, and Tb. Sp, SMI were significantly lower. Conclusions Significant bone loss and deteriorated mechanical properties of femur can be observed in animal model of osteoporosis induced by OVX combined with D-galactose. Red yeast rice cap-sules containing coenzyme Q10 show effective prevention effects. Furthermore, red yeast rice capsules(0. 5 tab-let·kg-1 ) have better effect on increasing the number of trabecular bone than diethylstilbestrol ( 30 μg · kg-1 ) does.

Effects of diethylstilbestrol on testicular oxidative stress and steroidogenesis in male rats / 中国比较医学杂志

Objective It is well known that diethylstilbestrol ( DES ) can result in testicular oxidative injury , and one of its mechanisms of action is leading to dysfunction of steroidogenesis .The aim of this study was to investigate the relationship between testicular oxidative injury caused by DES and the key synthetase activities for the synthesis pathway of steroidogenesis and the possible mechanism .Methods Twenty-four 4-wk-old male Wistar albino rats were randomly divided into 4 groups , 6 rats each.Three doses of DES (0.1, 1.0 and 10 μg/kg· d) groups and a vehicle (corn oil) control group , were respectively administered by subcutaneous injection once a day for eight weeks .The rats were sacrificed after 8 weeks treatment and the body weight , testis, epididymis, prostate were weighed, respectively.The testicular tissues were homogenized and the oxidation of MDA and ROS , the activity changes of antioxidases SOD, CAT and GPx, as well asthe activities of steroid synthetases 3β-HSD1 and 17β-HSD3 were determined by biochemical measurement.The levels oftestosterone and LH in peripheral blood were measured by radioimmunoassay .The intensities of expression of StAR,P450scc, 3β-HSD1, 17β-HSD3-mRNA were detected by PCR.Results In the 10.0 μg/kg dose group, the weights andorgan coefficients of testis and prostate were decreased significantly , the oxidation of MDA and ROS was increased distinctlyand the activities of SOD, CAT, GPx, 3β-HSD1 and 17β-HSD3 were reduced.The concentration of serum testosterone wasdecreased in the 10.0 μg/kg dose group.In the 10.0 μg/kg and 1.0 μg/kg dose groups, the decline of LH levelpresented a dose-dependent manner, and the intensities of immunochemical positive staining for StAR , P450scc, 3β-HSD1and 17β-HSD3 mRNA were decreased.Conclusions DES exposure results in disturbance of the oxidant /antioxidantbalance and decline of testosterone level that induces reproductive impairment in male rats .DES induces reductions of bothGPx and 3β-HSD activities which cause the decrease of testosterone synthesis .The expression of P450scc and 3β-HSDmRNA,which are the key synthetases in biosynthetic pathway of steroidogenesis , are inhibited by DES, and it isspeculated that the disturbance of steroidogenic synthesis enzymes may be one of the mechanisms of toxic effects of DES .

The observation and evaluation of bone histomorphometry in three osteoporosis models of mice / 中国药理学通报

Aim To investigate whether D-galactose cause osteoporosis and the difference compared with the osteoporosis induced by ovariectomy, and to deter-mine whether ovariectomy coupled with D-galactose ac-celerated the progress of osteoporosis and whether es-trogen had a preventive effect on these osteoporosis models. Methods Sixty SPF mice were randomly divided into six groups , namely sham-operated group, D-galactose group, OVX group, OVX + D-galactose group, OVX + D-galactose + diethylstilbestrol group and D-galactose + diethylstilbestrol group. Seventy days later, the right tibia was processed with undecal-cified sections for bone histomorphometric analysis. Results Compared with the sham-operated group, %Tb. Ar, Tb. Th and Tb. N decrease by 50. 4%, 25. 4%, 50. 9% ( P <0.01 ) respectively, Tb. Sp in-creased by 169. 4% (P <0.05), Oc. pm, Oc. No. ,%Oc. S, Oc. N/mm which reflected bone absorption significantly increased ( P < 0.01 ) , and % L. Pm, MAR, BFR/TV, BFR/BV, BFR/BS which reflected bone formation significantly decreased ( P <0.01 ) in OVX group. %Tb. Ar decreased by 30. 4% in D-ga-lactose group, but there was no statistically significant difference. However, the four parameters reflected the bone absorption in D-galactose group increased signifi-cantly ( P<0.05 ) , while the four parameters reflected bone formation decreased significantly ( P < 0.05 ) . OVX+D-galactose group has obvious performance of osteoporosis, but there was no significant difference compared to OVX group, nor to D-galactose group. Estrogen had significant preventive effect on related pa-rameters of osteoporosis induced by D-galactose and o-variectomy coupled with D-galactose. ConclusionsOsteoporosis model of mice can be established by OVX, D-galactose and OVX +D-galactose. Estrogen can effectively prevent bone loss induced by D-galac-tose and OVX+ D-galactose.

Prevention of osteopenia and dyslipidemia in rats after ovariectomy with combined aspirin and low-dose diethylstilbestrol / 生物医学与环境科学（英文）

<p><b>OBJECTIVE</b>To study whether effect of aspirin plus low-dose diethylstilbestrol is more effective and safer than high diethylstilbestrol dose alone on prevention of ovariectomy-induced osteopenia and dyslipidemia.</p><p><b>METHODS</b>Thirty-eight 4-month-old female SD rats were divided into baseline (BAS) group (n=6), sham operation group (n=8) and ovariectomy (OVX) group (n=24). The OVX group was further divided into vehicle treatment group (n=8), diethylstilbestrol (30 μg/kg•d) treatment group (OVX+D30 group, n=8), and aspirin (9 mg/kg•d) plus diethylstilbestrol (10 μg/kg•d) treatment group (OVX+A-D10 group, n=8). Their left tibiae were collected for the bone histomorphometric analysis in undecalcified sections. Left femurs were collected for the bone mineral density measurement.</p><p><b>RESULTS</b>The body weight and serum cholesterol were increased, while uterine weight and cancellous bone mass were decreased in OVX rats compared with the SHAM group. Cancellous bone mass was significantly increased, while body weight and bone resorption parameters were decreased in both A-D10 and D30 treatment group compared with OVX group. The rats treated with A-D10 showed significantly increased in bone formation parameters and decreased in serum triglyceride compared with the D30-treated rats.</p><p><b>CONCLUSION</b>Aspirin plus low-dose diethylstilbestrol can effectively prevent osteopenia by reducing bone resorption, and is thus a better treatment modality for preventing dyslipidemia than high-dose diethylstilbestrol alone.</p>

Tratamiento con dietilestilbestrol en pacientes refractarios a la castración por análogos LH- RH / Treatment with diethylstilbestrol in patients who had failed to androgen deprivation by lhrh agonists

Introducción: El objeto de este trabajo clínico es estudiar la eficacia de la administración de Dietilestilbestrol (DES) oral en pacientes con cáncer de próstata avanzado y que han presentado refractariedad al tratamiento con análogos LH-RH y además evaluar los efectos colaterales atribuibles a su uso. Material y métodos: Entre Noviembre de 2010 y Mayo de 2012 se ingresaron en forma consecutiva al estudio 15 pacientes con cáncer prostático avanzado, refractarios a manejo con análogos LH-RH. Edad promedio de los pacientes 69,4 años .Rango 57-80. Se registró el tipo de tratamiento realizado, detallando el manejo hormonal previo al que fueron sometidos. Se consideró refractariedad a los análogos, la detección de 2 alzas consecutivas del APE durante la administración de éstos. Se indicó a los pacientes 1mg. de DES al día. La evaluación del tratamiento se hizo cada 30 días con determinación de APE y registro de efectos colaterales. Resultados: De los 15 pacientes, 8 (53,3 por ciento) disminuyeron su APE inicial, 6 de ellos (40 por ciento) lo hicieron en más de un 50 por ciento de su valor y 2 (13,3 por ciento) disminuyeron el APE pero en menos de un 50 por ciento. 7 pacientes (46,6 por ciento) no disminuyeron su valor de APE y fueron considerados como fracasos. Como efectos colaterales del tratamiento tuvimos 13 pacientes (86,6 por ciento) que presentaron hipersensibilidad de los pezones, pero solo 2 requirieron tratamiento sintomático. 4 pacientes (26,6 por ciento) desarrollaron ginecomastia leve a moderada y no tuvimos ninguna complicación cardiovascular en los 15 pacientes estudiados. Conclusión: Consideramos de acuerdo a nuestros resultados que el DES oral es efectivo como tratamiento en los pacientes que han fallado o son refractarios a la deprivación androgénica por análogos LH-RH, con una baja morbilidad, buena aceptación de los pacientes y de muy bajo costo.

Introduction: The object of this clinical trial is to study the effectiveness of the administration of Diethylstilbestrol (DES) oral in patients with advanced cancer of prostate and that has presented resistance to the treatment with analogs LH-RH and in addition to evaluate the collateral effects attributable to its use. Material and methods: Between November of 2010 and May of 2012 15 patients with advanced prostate cancer, refractory to handling with analogs LH-RH entered themselves in consecutive form the study. Age average of the patients 69, 4 years, Rank 57-80. The type of made treatment was registered, detailing previous the hormonal handling which they were put under. Resistance to the analogs, the detection of 2 consecutive rises of the PSA was considered during the administration of this one. 1 mg. was indicated to the patients of DES to the day. The evaluation of the treatment was made every 30 days with determination of PSA and registry of collateral effects. Results: Of the 15 patients, 8 (53,3 percent) diminished their initial PSA, 5 of them (40 percent)did in more of a 50 percent of their value and 2 (13,3 percent) diminished the PSA but in less of a 50 percent. 7 patients (46,6 percent) did not diminished their value of PSA and were considered like failures. As collateral effects of the treatment we had 13 patients (86,6 percent) who presented hypersensitivity of the nipples, but single 2 required symptomatic treatment, 4 patients (26,6 percent) developed ginecomastia weighs moderate and we did not have any cardiovascular complication in the 15 studied patients. Conclusion: We considered according to our results that the oral DES is effective like treatment in the patients who have failed or ar refractory to the androgenic deprivation by analogs LH-RH, with a low morbidity, good acceptance of the patients and very low cost.

Spectrophotometric detection of diethylstilbestrol on the basis of the plasmon resonance absorption of silver nanoparticles / 西安交通大学学报·英文版

In this study, a spectrophotometric detection method for diethylstilbestrol (DES) was proposed by reducing silver nitrate (AgNO3) to obtain silver nanoparticles (AgNPs) in the medium of ammonia and sodium hydroxide. It was found that the resulting AgNPs have plasmon resonance absorption (PRA) characteristic at 415 nm, and the PRA is proportional to the increase of DES concentration in the range of 4.0 × 10-8 -1.0 × 10 -5 M with the detection limit (3σ) of 1.2 × 10 -7 M. Most of the coexisting substances at high concentrations did not affect the detection of real samples, such as tablets. The recovery was in the range of 96.01 %-107.41% and the RSD was lower than 4.7 %. This method can be successfully applied to control preparation quality of DES.

Spectrophotometric detection of diethylstilbestrol on the basis of the plasmon resonance absorption of silver nanoparticles / 药物分析学报

In this study, a spectrophotometric detection method for diethylstilbestrol (DES) was proposed by reducing silver nitrate (AgNO3) to obtain silver nanoparticles (AgNPs) in the medium of ammonia and sodium hydroxide. It was found that the resulting AgNPs have plasmon resonance absorption (PRA) characteristic at 415 nm, and the PRA is proportional to the increase of DES concentration in the range of 4.0×10-8-1.0×10-5M with the detection limit (3σ) of 1.2×10-7M. Most of the coexisting substances at high concentrations did not affect the detection of real samples, such as tablets. The recovery was in the range of 96.01%-107.41% and the RSD was lower than 4.7%. This method can be successfully applied to control preparation quality of DES.

A case of clear cell carcinoma of uterine cervix not related to intrauterine dietylstilbesterol exposure / 대한산부인과학회지

Clear cell carcinoma of the uterine cervix is rare cancer that accounts for 4 to 9% of the adenocarcinoma of uterine cervix. Although intrauterine exposure to diethylstilbestrol (DES) during early pregnancy is one of the established risk factors, DES exposure may not be confirmed in all patients. We experienced a case of clear cell carcinoma in the uterine cervix of 67-year-old woman who was not exposed to DES. She was initially diagnosed as endometrial clear cell carcinoma because of the normal colposcopic finding and histologically proven clear cell carcinoma from endometrial aspiration biopsy and endocervical curettage. We performed a total laparoscopic hysterectomy with bilateral salpingo-oophorectomy and lymphadnectomy including both pelvic and para-aortic regions. On the final pathologic diagnosis of clear cell carcinoma confined to endocervix, the patient was received adjuvant concurrent chemoradiation with weekly cisplatin. We present the case with a brief review of related literature.

Animal model for age- and sex-related genotoxicity of diethylstilbestrol

Environmental xenoestrogens pose a significant health risk for all living organisms. There is growing evidence concerning the different susceptibility to xenoestrogens of developing and adult organisms, but little is known about their genotoxicity in pre-pubertal mammals. In the present study, we developed an animal model to test the sex- and age-specific genotoxicity of the synthetic estrogen diethylstilbestrol (DES) on the reticulocytes of 3-week-old pre-pubertal and 12-week-old adult BALB/CJ mice using the in vivo micronucleus (MN) assay. DES was administered intraperitoneally at doses of 0.05, 0.5, and 5 µg/kg for 3 days and animals were sampled 48, 72 and 96 h, and 2 weeks after exposure. Five animals were analyzed for each dose, sex, and age group. After the DES dose of 0.05 µg/kg, pre-pubertal mice showed a significant increase in MN frequency (P < 0.001), while adults continued to show reference values (5.3 vs 1.0 MN/1000 reticulocytes). At doses of 0.5 and 5 µg/kg, MN frequency significantly increased in both age groups. In pre-pubertal male animals, MN frequency remained above reference values for 2 weeks after exposure. Our animal model for pre-pubertal genotoxicity assessment using the in vivo MN assay proved to be sensitive enough to distinguish age and sex differences in genome damage caused by DES. This synthetic estrogen was found to be more genotoxic in pre-pubertal mice, males in particular. Our results are relevant for future investigations and the preparation of legislation for drugs and environmentally emitted agents, which should incorporate specific age and gender susceptibility.

Fertility-sparing radical abdominal trachelectomy for cervical clear cell adenocarcinoma unrelated to diethylstilbestrol exposure : A case report / 대한산부인과학회지

Clear cell adenocarcinoma (CCAC) is a rare cancer that comprises less than 9% of the cervical adenocarcinoma cases. We experienced a case of fertility-sparing radical abdominal trachelectomy for cervical clear cell adenocarcinoma (CCAC). Thus, reported it. A 27 year old female was diagnosed with clinical stage Ib cervical CCAC. She had no history of maternal exposure to diethylstilbestrol and had negative PAP cytology and HPV tests. She was treated with neoadjuvant chemotherapy followed by radical abdominal trachelectomy. After 2 cycles of postoperative adjuvant chemotherapy, the lesion disappeared completely in an imaging study, and potential fertility was preserved. Radical abdominal trachelectomy with chemotherapy may be a valuable approach for treating stage Ib cervical CCAC in women that wish to preserve potential fertility.

Priapismo na doença falciforme / Sickle cell priapism

Priapismo é a complicação relativamente freqüente na doença falciforme. Consiste de ereção peniana prolongada e dolorosa, não acompanhada de desejo ou estímulo sexual, usualmente persistente por mais de quatro horas. A disfunção erétil é seqüela comum no tratamento inadequado. A forma típica de priapismo nestes pacientes é a de baixo fluxo, ocorrendo, ainda, a forma de priapismo recorrente ou stuttering. O tratamento inicial para esta complicação ainda não está bem estabelecido. São propostas várias opções medicamentosas, tais como agonistas adrenérgicos, hormônios análogos à gonadotrofina, dietil-estilbestrol, hidroxiuréia entre outras. Nos casos de falha com as medidas conservadoras e medicamentosas, a intervenção cirúrgica, com confecção de shunt cavernoso, é necessária. Este estudo revisa a incidência, patogênese e opções terapêuticas desta complicação na doença falciforme.

Priapism is a common complication of sickle cell disease. It is defined as a painful and persistent penil erection not accompanied by sexual desire or stimulation, usually lasting for more than 4 hours. The typical forms of priapism in sickle cell disease are low-flow and recurrent priapism (stuttering). The first-line treatment for this complication is not totally clear. Several treatments have been proposed such as adrenergic agents, gonadotropin-releasing hormone analogues, diethylstilbestrol, hydroxyurea. If conservative treatments fail, surgical intervention is required with cavernous shunts. This study reviewed the incidence, pathogenesis and management of sickle cell priapism.

The change of the mRNA expression of INSL3 gene in perinatal mice leydig cells exposed to diethylstilbestrol in vivo and in vitro / 重庆医科大学学报

Objective:To explore the mRNA expression of INSL3 gene in perinatal mice Leydig cells exposed to diethylstilbestrol(DES) in vivo and in vitro.Methods:The Leydig cells were isolated from fetal mouse testis and were cultured in DMEM/F12 medium and identified by 3 beta-hydroxysteroid dehydrogenase(3?-HSD).Reverse transcriptase-polymerase chain reaction(RT-PCR)and in situ hybridization were used for examination of the expression levels of INSL3 mRNA in primarily cultured Leydig cells incubated with DES(at the dose of 1?g/L,5?g/L and 25?g/L,respectively).Pregnant mice were exposed to DES at the dose of 1,10 or 100?g/kg body weight per day by gavage from gestation day(GD)12 to postnatal day(PND)3.The expression of INSL3 gene in neonatal mouse testis was investigated by RT-PCR.Results:Histological alterations of primarily cultured Leydig cells and neonatal mouse testis exposed to DES were observed.The expression level of INSL3 mRNA in DES treated groups including the primarily cultured Leydig cells and male mouse offspring’s testis were lower than those of the control groups.Conclusion:DES can downregulate the expression level of INSL3 mRNA in Leydig cells in vitro and in vivo.It may be a possible mechanism that DES interferes with gubernaculum development and cause cryptorchidism.

DYNAMIC EFFECT OF ADMINISTERING DIETHYLSTILBESTROL EXTERNALLY TO NEONATAL FEMALE BALB/c MICE ON THE EXPRESSION OF ESTROGEN RECEPTOR IN MICE SPLEENS / 解剖学报

Objective To investigate the dynamic changes of estrogen receptors (ER) in spleen of female BALB/c mice after injected with diethylstilbestrol (DES) beginning in neonatal period. Methods Neonatal female BALB/c mice were injected subcutaneously on cervix-backside with DES within 24 hours after birth at intervals of 24 hours for 5 times. Control groups were injected with olive oil with the same method. Mice were killed on 7 days, 14 days, 21 days, 35 days and 49 days after birth separately, the spleen was taken out, imbedded with paraffin and sectioned serially in 5??m. The expression of ER in slice of spleen was detected by immunohistochemistry technique. Results ER positive cells were present in both DES-injected groups and control groups. ER positive cells were mostly lymphocytes. A correlation between age and the intensity of positive reactions was showed in both groups. The intensity of ER immunohistochemistry positive reaction in DES group was much stronger than that in control group, and there was a significant statistic difference between the two groups. Conclusion The ER expression exists in spleen of female BALB/c mice and increases with the age of mice. The contact of DES in neonatal female BALB/c mice will lead to an increased ER expression in their spleens and this effect can continue to their manhood at least.

Preparation and Quality Control of Lomefloxacin Hydrochloride and Diethylstibestrol Oil / 中国药房

OBJECTIVE:To prepare lomefloxacin hydrochloride and diethylstilbestrol oil and to establish the method for its quality control.METHODS:The content of lomefloxacin was determined by UV-spectrophotometry at the wavelength of283nm.RESULTS:The detected concentration of lomefloxacin hydrochloride was in linear relation to absorptivity in the range of2.5～16.0?g/ml(r=0.9995,n=6).The average recovery was99.8%(RSD=0.74%).CONCLUSION:The preparation technique is simple and the method for quality control is feasible.

The effects of epimedium pubescens flavonoids combined with diethylstilbestrol on ovariectomy induced osteopenia in rats / 中国药理学通报

AIM To determine whether epimedium pubescens flavonoids(EF) in combination with diethylstilbestrol(DES) can completely prevent bone loss in ovariectomized rats. METHODS Sixty Sprague-Dawley female rats at age of 4 months were divided into six groups. Ten rats were sacrificed at age of 4.5 months before operation. The other rats were sham-operated and treated orally with vehicle or ovariectomized (OVX) and treated orally with either vehicle, or diethylstilbestrol(DES) at 22.5 ?g?kg -1 ?d -1 , or EF at 300 mg?kg -1 ?d -1 , or EF 300 mg?kg -1 ?d -1 in combination with DES 22.5 ?g?kg -1 ?d -1 for 90 days. Double in vivo fluorochrome labeling was administrated. The undecalcified longitudinal proximal tibial metaphyseal sections were used for [FQ(9*2。46,X-WZ]-the bone histomorphometric analysis. RESULTS DES prevented OVX-induced bone loss and decreased body weight gain and total serum cholesterol,but it increased uterine luminal epithelial thickness.Combination of EF with DES completely prevented OVX-induced bone loss and did not increase uterine luminal epithelial thickness.The effect of the combination in preventing bone loss was more significant than that of DES. CONCLUSION EF in combination with DES showed synergistic effect on prevention of osteoporosis induced by ovariectomy.-

CHANGES ON EXPRESSION OF bcl-2,p53 AND CADHERIN IN ADULT HAMSTER SPERMATOGENIC CELLS DURING DES INDUCING ABNORMAL SPERMATOGENESIS / 解剖学报

Objective To prove the mechanism of diethylstibestrol(DES) induced abnormal spermatogenesis,this study on the changes of proto-oncogenes bcl-2 and p53 proteins as well as cadherin adherens molecules expression in adult male hamster spermatogenic cells. Methods Adult male golden hamsters were treated daily olive oil vehicle either alone(control)or containing 1 mg/kg body weight of DES (experiment)by subcutaneous injection for 7 days.The changes of testes histological morphology were observed under light and electron microscope.The expressions of bcl-2 and p53 and cadherin in the testes seminiferous epithelium were detected by immunohistochemistry. Results DES induced adult hamster testes abnormal spermatogenesis.As compared to the control group animals,in DES-treated group animals the expression of both bcl-2 and p53 significantly increased in spermatogenic cells,especially in spermatocytes and round spermatids.However,the expression of cadherin adherens molecules obviously decreased.Conclusion It is one of reasons of DES inducing abnormal spermatogenesis that DES can result in increasing in the expression of proto-oncogenes bcl-2 and p53,and reducing cadherin adherens molecules expression.