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diethylstilbestrol diethylstilbestrol [keywords]
- Influence of exercise on bone remodeling-related hormones and cytokines in ovariectomized rats: a model of postmenopausal osteoporosis. [Journal Article]
- PLoS One 2014; 9(11):e112845.
This study aims to explore the effects of exercise on postmenopausal osteoporosis and the mechanisms by which exercise affects bone remodeling. Sixty-three Wistar female rats were randomly divided into five groups: (1) control group, (2) sham-operated group, (3) OVX (Ovariectomy) group, (4) DES-OVX (Diethylstilbestrol-OVX) group, and (5) Ex-OVX (Exercise-OVX) group. The rat osteoporosis model was established through ovariectomy. The Ex-OVX rats were made to run 251.2 meters every day, 6 d/wk for 3 months in a running wheel. Trabecular bone volume (TBV%), total resorption surface (TRS%), trabecular formation surface (TFS%), mineralization rate (MAR), bone cortex mineralization rate (mAR), and osteoid seam width (OSW) were determined by bone histomorphometry. The mRNA and protein levels of interleukin-1β (IL-1β2), interleukin-6 (IL-6), and cyclooxygenase-2 (Cox-2) were determined by in situ hybridization and immunohistochemistry, respectively. Serum levels of estrogen estradiol (E2), calcitonin (CT), osteocalcin (BGP), and parathyroid hormone (PTH) were determined by ELISA assays. The investigation revealed that compared to the control and the sham-operated groups, the OVX group showed significantly lower levels of TBV%, E2, and CT, but much higher levels of TRS%, TFS%, MAR, OSW, BGP, and PTH. The Ex-OVX group showed increased TBV% and serum levels of E2 and CT compared to the OVX group. Ovariectomy also led to a significant increase in IL-1β mRNA and protein levels in the bone marrow and IL-6 and Cox-2 protein levels in tibias. In addition, the Ex-OVX group showed lower levels of IL-1 mRNA and protein, IL-6 mRNA, and Cox-2 mRNA and protein than those in the OVX group. The upshot of the study suggests that exercise can significantly increase bone mass in postmenopausal osteoporosis rat models by inhibiting bone resorption and increasing bone formation, especially in trabecular bones.
- Anogenital distance (AGD) plasticity in adulthood: Implications for its use as a biomarker of fetal androgen action. [JOURNAL ARTICLE]
- Endocrinology 2014 Nov 6.:en20141534.
Androgen action during the fetal masculinization-programming window (MPW) determines the maximum potential for growth of androgen-dependent organs (e.g. seminal vesicles, prostate, penis, perineum) and is reflected in anogenital distance (AGD). As such, determining AGD in postnatal life has potential as a lifelong easily accessible biomarker of overall androgen action during the MPW. However, whether the perineum remains androgen-responsive in adulthood and thus responds plastically to perturbed androgen drive remains unexplored. To determine this, we treated adult male rats with either the anti-androgen Flutamide, or the estrogen Diethylstilbestrol (DES) for five weeks, followed by a four-week wash-out period of no treatment. We determined AGD, and its correlate anogenital index (AGI; AGD relative to bodyweight), at weekly intervals across this period and compared this to normal adult rats (male and female), castrated male rats, and appropriate vehicle controls. These data showed that, in addition to reducing circulating testosterone and seminal vesicle weight, castration significantly reduced AGD (by ∼17), demonstrating that there is a degree of plasticity in AGD in adulthood. Flutamide treatment increased circulating testosterone yet also reduced seminal vesicle weight due to local antagonism of androgen receptor. Despite this suppression, surprisingly, Flutamide treatment had no effect on AGD at any time-point. In contrast, whilst DES treatment suppressed circulating testosterone and reduced seminal vesicle weight, it also induced a significant reduction in AGD (by ∼11%), which returned to normal one week after cessation of DES treatment. We conclude that AGD in adult rats exhibits a degree of plasticity, which may be mediated by modulating local androgen/estrogen action. The implications of these findings regarding the use of AGD as a life-long clinical biomarker of fetal androgen action are discussed.
- Effect of 1,25-dihydroxyvitamin d3 on regulatory T cells in ovariectomized mice. [Journal Article]
- Biomed Environ Sci 2014 Oct; 27(10):779-85.
To investigate the correlation between regulatory T (Treg) cells and postmenopausal osteoporosis and the antiosteoporotic effect of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in relation to Treg cells.Fifty female BALB/c mice were randomly divided into five groups: the basal control (BAS), Sham, ovariectomy (OVX), OVX+diethylstilbestrol (OVX+DES), and OVX+1,25(OH)2D3. Tibias were harvested and processed with decalcification for quantitative bone histomorphometry. Femurs were stained by immunohistochemistry to detect Foxp3 protein expression. Spleens were used to detect Treg and Foxp3 gene expression by flow cytometry and quantitative RT-PCR, respectively.In comparison with the Sham group, a significant decrease was found in the OVX group in such indices as trabecular bone volume/total tissue area (BV/TV), trabecular number (Tb.N) and trabecular thickness (Tb.Th). 1,25(OH)2D3 and DES partly prevented the decrease in BV/TV, Tb.N, Tb.Th in OVX mice. Treg cell number, Foxp3 mRNA expression in spleen and Foxp3 protein expression in femur significantly decreased in the OVX-treated group compared with those in the sham group. 1,25(OH)2D3 and DES significantly increased Treg cell number and Foxp3 expression. Treg cells and Foxp3 gene expression were related to bone histomorphometric parameters.The decrease in Treg cell numbers is relevant to the postmenopausal osteoporosis. The antiosteoporosis of 1,25(OH)2D3 is related to regulatory T cells.
- [Isolation, identification and characterization of a diethylstilbestrol-degrading bacterial strain Serratia sp]. [English Abstract, Journal Article]
- Huan Jing Ke Xue 2014 Aug; 35(8):3169-74.
Utilizing the diethylstilbestrol (DES)-degrading bacteria to biodegrade DES is a most reliable technique for cleanup of DES pollutants from the environment. However, little information is available heretofore on the isolation of DES-degrading bacteria and their DES removal performance in the environment. A novel bacterium capable of degrading DES was isolated from the activated sludge of a wastewater treatment plant. According to its morphology, physiochemical characteristics, and 16S rDNA sequence analysis, this strain was identified as Serratia sp.. The strain was an aerobic bacterium, and it could degrade 68.3% of DES (50 mg x L(-1)) after culturing for 7 days at 30 degrees C, 150 r x min(-1) in shaking flasks. The optimal conditions for DES biodegradation by the obtained strain were 30 degrees C, 40-60 mg x L(-1) DES, pH 7.0, 5% of inoculation volume, 0 g x L(-1) of added NaCl, and 10 mL of liquid medium volume in 100 mL flask.
- Clear Cell Carcinoma of Cervix in a 60- year-old Woman: A Case Report. [Journal Article]
- J Clin Diagn Res 2014 Aug; 8(8):OD01-2.
Clear cell carcinoma of cervix is a rare entity amongst cervical neoplasms especially post diethylstilbestrol era. It is hypothesised to have a bimodal distribution with spontaneous cases unrelated to DES exposure observed in elderly age group. We report a rare case of clear cell carcinoma of cervix (CCCC) in a 60-year-old Asian female with no history of diethylstilbestrol (DES) ingestion. She underwent radical hysterectomy and adjuvant radiotherapy and showed no signs of recurrence even after 6 moths of follow up. Review of relevant literature was done including possible aetiology, appropriate treatment and prognostic factors.
- [Clear cell adenocarcinoma of the uterine cervix in a 17-year-old girl.] [JOURNAL ARTICLE]
- Ugeskr Laeger 2014 Sep 1; 176(36)
Clear cell adenocarcinoma of the uterine cervix (CCEA) is a rare disease, accounting for only 1% of all cervical cancers. The disease in young women is linked to diethylstilbestrol (DES) exposure in utero. Following the ban of DES in 1979, CCEA rarely occurs in young women, but still remains a challenge in diagnosis and fertility preservation. We report on a 17-year-old girl, unexposed to DES, diagnosed with clear cell adenocarcinoma in a cervical polyp.
- Assessment of estrogen disrupting potency in animal foodstuffs of China by combined biological and chemical analyses. [Journal Article]
- J Environ Sci (China) 2014 Oct 1; 26(10):2131-7.
Food has been documented as one of major routes for human exposure to environmental estrogens (EEs), but information on the occurrence of EEs in animal foodstuffs is still scarce. This study analyzed estrogenic activity in 16 types of animal foodstuffs (n=142) collected from four cities (Wuhan, Guangzhou, Wenzhou and Yantai) of China by combined yeast estrogen screen (YES) bioassay and chemical analysis. By bioassay, all samples' extracts were found to induce estrogenic activities and the bioassay-derived 17β-estradiol equivalent (EEQbio) ranged from 8.29 to 118.32ng/g. In addition, the samples were analyzed by liquid chromatography coupled to tandem mass spectrometry for further chemical analysis. 17β-Estradiol was found in all samples in this survey at levels of 0.44 to 15.04ng/g. All samples had 33.1% detection rate of 17α-ethinylestradiol (EE2), and the maximum concentration was 2.80ng/g. Bisphenol A and 4-nonylphenols were detected in 83.8% and 83.1% of samples, with concentrations up to 12.56ng/g and 35.76ng/g, respectively. However, the concentrations of estrone, diethylstilbestrol and 4-t-octylphenol were found to be below the limit of detection. A comparison of EEQbio measured from the YES assay and EEQchem calculated from chemical analysis showed good correlation (R(2)=0.84). Based on the results, the YES assay can be used as a rapid pre-screening method for monitoring the levels of estrogenic activity in large numbers of animal foodstuffs, and chemical analysis used in combination can be used for the identification of specific EEs.
- Diallyl sulfide inhibits diethylstilbestrol induced DNA damage in human breast epithelial cells (MCF-10A). [JOURNAL ARTICLE]
- Steroids 2014 Sep 30.
Breast cancer is the second leading cause of cancer deaths in women in the United States. Diethylstilbestrol (DES) is a synthetic estrogen that has been shown to cause cancer in animals and humans, altering cell viability as well as inducing DNA damage. Diallyl sulfide (DAS) is a garlic organosulfide that has been shown to inhibit both the initiation and promotion phases of cancer in vivo and in vitro, as well as reduce the risk of cancer in epidemiological studies. MCF-10A cells, regarded as a normal breast epithelial cell line, were treated with varying concentrations of DES, DAS or various dose combinations of DES and DAS concomitantly, and assessed for cell viability, DNA strand breaks, and lipid peroxidation. DES (10μM) in combination with 1, 10, or 100μM DAS resulted in a 31%, 34%, or 36% respective increase in cell viability compared to the DES treatment alone, after 24h. At the same time point, 1, 10, and 100μM DAS were all effective in significantly reducing DES (100μM)-induced strand breaks to near that of the vehicle control. Additionally, 1μM DAS was effective in significantly reducing DES (100μM)-induced lipid peroxidation after 3h. The results of this research suggest that DAS is effective in recovering cell viability, attenuating DNA strand breaks, and decreasing lipid peroxidation in MCF-10A cells.
- Estrogens in the wrong place at the wrong time: fetal BPA exposure and mammary cancer. [JOURNAL ARTICLE]
- Reprod Toxicol 2014 Sep 29.
Iatrogenic gestational exposure to diethylstilbestrol (DES) induced alterations of the genital tract and predisposed individuals to develop clear cell carcinoma of the vagina as well as breast cancer later in life. Gestational exposure of rodents to a related compound, the xenoestrogen bisphenol-A (BPA) increases the propensity to develop mammary cancer during adulthood, long after cessation of exposure. Exposure to BPA during gestation induces morphological alterations in both the stroma and the epithelium of the fetal mammary gland at 18 days of age. We postulate that the primary target of BPA is the fetal stroma, the only mammary tissue expressing estrogen receptors during fetal life. BPA would then alter the reciprocal stroma-epithelial interactions that mediate mammogenesis. In addition to this direct effect on the mammary gland, BPA is postulated to affect the hypothalamus and thus in turn affect the regulation of mammotropic hormones at puberty and beyond.
- Liquid-phase exfoliated graphene as highly-sensitive sensor for simultaneous determination of endocrine disruptors: Diethylstilbestrol and estradiol. [JOURNAL ARTICLE]
- J Hazard Mater 2014 Sep 18.:157-163.
It is quite important to develop convenient and rapid analytical methods for trace levels of endocrine disruptors because they heavily affect health and reproduction of humans and animals. Herein, graphene was easily prepared via one-step exfoliation using N-methyl-2-pyrrolidone as solvent, and then used to construct an electrochemical sensor for highly-sensitive detection of diethylstilbestrol (DES) and estradiol (E2). On the surface of prepared graphene film, two independent and greatly-increased oxidation waves were observed at 0.28V and 0.49V for DES and E2. The remarkable signal enlargements indicated that the detection sensitivity was improved significantly. The influences of pH value, amount of graphene and accumulation time on the oxidation signals of DES and E2 were discussed. As a result, a highly-sensitive and rapid electrochemical method was newly developed for simultaneous detection of DES and E2. The values of detection limit were evaluated to be 10.87nM and 4.9nM for DES and E2. Additionally, this new method was successfully used in lake water samples and the accuracy was satisfactory.