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diethylstilbestrol diethylstilbestrol [keywords]
- G Protein-Coupled Estrogen Receptor-Protein Kinase A-ERK-CREB Signaling Pathway is Involved in the Regulation of Mouse Gubernaculum Testis Cells by Diethylstilbestrol. [JOURNAL ARTICLE]
- Arch Environ Contam Toxicol 2013 Dec 4.
The etiology of testicular dysgenesis syndrome is multifactorial and involves environmental factors, such as environmental estrogens. Several studies have shown that hormonal effects on the gubernaculum may affect testicular descent. Diethylstilbestrol (DES) is a nonsteroidal synthetic estrogen that disrupts the morphology and proliferation of gubernacular cells, but the underlying mechanisms remain elusive. In this study, we aimed to determine whether DES may regulate the function of gubernaculum testis cells by way of nongenomic effects mediated by G protein-coupled estrogen receptor (GPER). We used cultured mouse gubernacular testis cells to demonstrate that GPER is expressed in gubernaculum testis cells. Erk1/2 inhibitor PD98059, PKA inhibitor H89, and Src inhibitor PP2 relieved DES-induced inhibition of gubernaculum testis cell proliferation, but ER inhibitor ICI 182780 had no effects on DES-induced inhibition of gubernaculum testis cell proliferation. In addition, we found that DES induced the activation of CREB downstream of PKA, Src, and ERK1/2 in these cells. These data suggest that the effects of DES on mouse gubernaculum testis cells are mediated at least partially by GPER-protein kinase A-ERK-CREB signaling pathway.
- Analysis of oestrogenic compounds in dairy products by hollow-fibre liquid-phase microextraction coupled to liquid chromatography. [Journal Article]
- Food Chem 2014 Apr 15.:319-25.
In this work, the potential of a hollow-fibre liquid-phase microextraction (LPME)-based method has been studied and validated for the extraction of a group of nine oestrogenic compounds four of them being natural (oestriol, 17β-oestradiol, 17α-oestradiol and oestrone), four being synthetic (17α-ethynyloestradiol, diethylstilbestrol, dienestrol and hexestrol) and one metabolite (2-hydroxyoestradiol) in different dairy products (whole and skimmed natural yogurt, a probiotic yogurt-type drink and cheese). The methodology includes a prior protein precipitation with acidified acetonitrile for all samples and an additional defatting step with n-hexane for cheese, the matrix with the highest fat content. Later separation, determination and quantification were done by high-performance liquid chromatography coupled to a diode array detector and a fluorescence detector set in series. Calibration, sensitivity, precision and accuracy of the method were carried out in the selected matrices, providing good linearity, LODs in the low μg/kg or μg/L range, good precision and appropriate accuracy.
- Electrochemical sensor based on magnetic molecularly imprinted nanoparticles at surfactant modified magnetic electrode for determination of bisphenol A. [JOURNAL ARTICLE]
- Biosens Bioelectron 2013 Nov 13.:258-261.
A selective electrochemical sensor based on magnetic molecularly imprinted nanoparticles was developed for determination of bisphenol A (BPA). The particles with regular morphology, high saturation magnetization and good monodispersion were prepared. The hydrophilicity, sensitivity and anti-fouling of the sensor were enhanced by modifying carbon paste electrode with surfactant CTAB in advanced. The results demonstrated that the response of BPA on imprinted electrode was 2.6 times as much as that on non-imprinted sensor. Moreover, the separation factors of BPA to β-estradiol, estriol and diethylstilbestrol were 16.5, 17.3 and 6.6, respectively. Under optimized conditions, the currents were found to be proportional to the BPA concentrations in the range of 6.0×10(-7)-1.0×10(-4)mol/L with a detection limit of 1.0×10(-7)mol/L (S/N=3). A rapid response of the imprinted sensor was obtained within 3min. The developed sensor was successfully used for determination of BPA in actual samples such as drink bottles and lake water.
- Early exposure of 17α-ethynylestradiol and diethylstilbestrol induces morphological changes and alters ovarian steroidogenic pathway enzyme gene expression in catfish, Clarias gariepinus. [JOURNAL ARTICLE]
- Environ Toxicol 2013 Nov 25.
Environmental estrogens are major cause of endocrine disruption in vertebrates, including aquatic organisms. Teleosts are valuable and popular models for studying the effects of endocrine disrupting chemicals (EDCs) in the environment. In the present study, we investigated the changes caused by exposure to the synthetic estrogens 17α-ethynylestradiol (EE2 ) and diethylstilbesterol (DES) during early stages of growth and sex differentiation of air-breathing catfish, Clarias gariepinus, at the morphological, histological, and molecular levels. Catfish hatchlings, 0 day post hatch (dph) were exposed continuously to sublethal doses of EE2 (50 ng/L) and DES (10 ng/L) until 50 dph and subsequently monitored for ovarian structural changes and alteration in the gene expression of steroidogenic enzymes till adulthood. Treated fish exhibited morphological deformities such as spinal curvature, stunted growth, and yolk-sac fluid retention. In addition to ovarian atrophy, DES-treated fish showed either rudimentary or malformed ovaries. Detailed histological studies revealed precocious oocyte development as well as follicular atresia. Further, transcript levels of various steroidogenic enzyme and transcription factor genes were altered in response to EE2 and DES. Activity of the rate-limiting enzyme of estrogen biosynthesis, aromatase, in the ovary as well as the brain of treated fish was in accordance with transcript level changes. These developmental and molecular effects imparted by EE2 and DES during early life stages of catfish could demonstrate the deleterious effects of estrogen exposure and provide reliable markers for estrogenic EDCs exposure in the environment. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.
- Indole-3-carbinol attenuates the deleterious gestational effects of bisphenol A exposure on the prostate gland of male F1 rats. [JOURNAL ARTICLE]
- Reprod Toxicol 2013 Nov 17.:56-66.
Bisphenol A (BPA) is a chemical that has been investigated for it potential to cause prostate diseases. In this study, pregnant Sprague-Dawley rats were treated with 25 or 250μg/kg BPA from gestational day (GD) 10 to GD21 with or without concurrent indole-3-carbinol (I3C) feeding. I3C is a phytochemical, and it affords chemoprotection against many types of neoplasia. Male F1 rats from different litters were euthanized on post-natal day (PND) 21 and PND180. BPA-treated groups showed a significant increase in histopathological lesions, but I3C feeding reversed many of these changes, mainly at PND180. Maternal I3C feeding increased prostate epithelial apoptosis in the BPA-treated groups and across age groups. Furthermore, I3C induced partial normalization of the prostate histoarchitecture. The results pointed to a protective effect of maternal I3C feeding during pregnancy in the BPA-exposed male offspring, thereby indicating reduction in the harmful effects of gestational BPA imprinting on the prostate.
- The effects of diethylstilbestrol administration on rat kidney. Ultrastructural study. [Journal Article]
- Saudi Med J 2013 Nov; 34(11):1114-24.
To assess the histological and ultrastructural changes that can be induced by diethylstilbestrol (DES) on renal tissues using histological, immunohistochemical, and ultrastructural methods.Thirty adult male Wistar rats were divided into 3 groups (10 rats each): Group 1 - control; Group 2 - received DES at a dose of 60 ug/kg/day, dissolved in 0.1 ml corn oil for 20 days; and Group 3 - received the same dose of DES for 50 days by oral gavage. The renal tissues were studied histologically, immunohistochemically (using an anti-BCL2-associated X protein [BAX protein] antibody), and ultrastructurally. This study was carried out at the Anatomy Department, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia between December 2011 and December 2012.The DES administration for 50 days caused noticeable degeneration, and alteration of the morphology of the renal tissues in the form of damaged renal tubules with loss of the brush border of the proximal convoluted tubules and increased cellularity of the glomeruli. In addition, there was a significant increase in BAX protein expression based on immunoreactivity, and in renal tubules, as well as glomerular cells. These changes were less obvious after 20 days of treatment.Non-steroidal, synthetic estrogens showed harmful effects on the renal tissues and altered their morphology with an increased number of apoptotic cells, and these changes were duration dependent.
- Menarche, Menopause, Years of Menstruation, and the Incidence of Osteoporosis: The Influence of Prenatal Exposure to Diethylstilbestrol. [JOURNAL ARTICLE]
- J Clin Endocrinol Metab 2013 Nov 18.
Context.Estrogen is critical for bone formation and growth in women. Estrogen exposures occur throughout life, including prenatally, and change with reproductive events, such as menarche and menopause.Objective.The objective of this study was to investigate the association between age at menarche, age at menopause, and years of menstruation with incidence of osteoporosis and assess the impact of prenatal exposure to diethylstilbestrol (DES), a synthetic estrogen, on such associations.Design, Setting, and Participants.Participants were 5,573 women in the National Cancer Institute Combined Cohort Study of DES (1994-2006). Data on reproductive history and medical conditions were collected through questionnaires at baseline in 1994 and subsequently in 1997, 2001, and 2006. Age-stratified Cox regression models were used to calculate multivariable incidence rate ratios (IRR) and 95% confidence intervals (CI). Effect measure modification by prenatal DES exposure was assessed using cubic restricted spline regression models.Main Outcome Measure(s).OsteoporosisResults.The IRRs for osteoporosis incidence with age at menarche <11 years and age at menopause ≥50 years were 0.82 (CI: 0.59, 1.14) and 0.61 (CI: 0.40, 0.92), respectively. Fewer than 25 years of menstruation was associated with an increased incidence of osteoporosis (IRR: 1.80; CI: 1.14, 2.86) compared with ≥ 35 years of menstruation. Associations were stronger among women who had not been prenatally exposed to DES.Conclusions.Our data support the hypothesis that lifetime cumulative exposure to estrogens is protective against osteoporosis. Furthermore, prenatal exposure to estrogen appears to modify these associations, although the mechanism by which this occurs is unknown.
- Diethylstilbestrol for the treatment of patients with castration-resistant prostate cancer: Retrospective analysis of a single institution experience. [Journal Article]
- Oncol Rep 2014 Jan; 31(1):428-34.
The aim of the present retrospective study was to evaluate the efficacy and safety of diethylstilbestrol (DES) as treatment for patients with castration-resistant prostate cancer (CRPC) and to identify predicting factors of response to DES. Patients treated with DES during the castration-resistant phase following the failure of prior treatment with LH-RH analogs during the castration-sensitive phase were retrieved from a prostate cancer database of our institution. Patients were treated with a daily dose of DES of 1-4 mg (mean, 2.6 mg) and anticoagulants for thromboembolic prophylaxis until disease progression. We analyzed their medical records, biochemical prostate-specific antigen (PSA) response and time to disease progression (TDP). Disease response and progression were identified according to the PCWG2 criteria. Patient data were examined using Kaplan-Meier survival analysis and statistical correlation tests with intra-patient comparison of the LH-RH and DES treatment phases. Forty-three DES-treated CRPC patients were found in our database through July 2011. The median age was 66 years. Sixty-three percent of the patients achieved a ≥50% decline in their serum PSA levels during DES therapy. Median TDP was 20.4 months for LH-RH analog treatment in the castration-sensitive phase, and 7.1 months for DES treatment in the castration-resistant phase. Durable responses (>1 year) were observed in 31% of the patients. Median overall survival was 57 months from the start of the DES therapy. There was no significant correlation between the TDP under LH-RH analogs and under DES therapy among the 38 patients eligible for correlation analysis. However, the magnitudes of serum PSA responses under DES and LH-RH analogs were significantly correlated with each other, and with the TDP under DES therapy. There were no treatment-related deaths. Four patients (9%) developed thromboembolic complications while under treatment, some of which appeared to be related to a discontinuation of thromboprophylaxis. In conclusion, DES confers substantial clinical benefit in the treatment of CRPC, with a relatively good safety profile when administered with thromboprophylaxis. The use of DES may be effective in CRPC, irrespective of the length of the hormone-sensitive period with LH-RH treatment. The magnitude of PSA response to previous treatment with LH-RH analogs, as well as to DES, was predictive of the duration of response to DES.
- Vaginal laparoscopically assisted radical trachelectomy in cervical clear cell adenocarcinoma. [Journal Article]
- Ecancermedicalscience 2013.:373.
Adenocarcinoma of the cervix is a rare condition that has shown an increase in incidence, especially in the 20- to 34-year-old group. Adenocarcinoma represents about 5-10% of all tumours in this area, and, among these, the clear cell type accounts for 4-9%. This type of tumour affects mainly postmenopausal women but also occurs in young women with a history of prenatal exposure to diethylstilbestrol (DES). The prognosis for adenocarcinoma of the cervix is poor overall and worse for the clear cell variety. This article discusses a case of clear cell adenocarcinoma of the cervix, unrelated to intrauterine exposure to DES, in a woman of childbearing age who wished to preserve her fertility and was therefore treated by radical vaginal trachelectomy and pelvic lymphadenectomy.
- Liquid chromatography-mass spectrometry method for the quantitative determination of residues of selected veterinary hormones in powdered ingredients derived from bovine milk. [Journal Article]
- J Agric Food Chem 2013 Dec 4; 61(48):11782-91.
A rugged, quantitative liquid chromatography-tandem mass spectrometry method with modified QuEChERS (quick, easy, cheap, effective, rugged, and safe) sample preparation for 17 selected veterinary hormones in six different powdered ingredients derived from bovine milk was developed and comprehensively validated. A universal post-extraction spiked matrix-matching approach based on whole milk powder has been successfully implemented. Three validation runs based on four levels of pre-extraction spiked quality control (QC) samples have been conducted. Overall accuracy (86-117%), overall precision (<20% RSD), selectivity, absolute extraction recovery (62-82%), matrix effect (<15% for most compounds), limits of detection (0.1-0.8 μg/kg, except for diethylstilbestrol at 3.8 μg/kg), limits of quantitation (0.2-2.0 μg/kg, except for diethylstilbestrol at 10.0 μg/kg), and extract stability (48 h) have been determined. The method is proposed for the routine analysis of hormones potentially present in powdered ingredients derived from bovine milk.