PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “DIETHYLSTILBESTROL”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 721 records · Page 40Linked to original sources
PubMedDate not supplied

Consequences of prenatal exposure to diethylstilbestrol.

Exposure to the drug diethylstilbestrol (DES) during the first 18 weeks of prenatal life can have many results ranging from benign misconfigurations of the reproductive organs to adenocarcinoma. Since the drug was routinely administered to pregnant American women from 1940 to 1970, a large population of Americans are involved. The key factor is early awareness to the exposure and careful follow-up. Since many of those exposed are unaware that they received DES, the health care profession must be attuned to the signs and symptoms predisposed by the exposure and be able to provide adequate follow-up and education concerning this medical problem.

Abnormalities, Drug-Induced↗
PubMed2000

Intrauterine exposure to diethylstilbestrol: long-term effects in humans.

DES is the most carefully scrutinized EDC and its history provides valuable insights into the current evaluation of less well-studied EDCs. This review summarizes the health effects of prenatal exposure to diethylstilbestrol (DES) and emphasizes the role of DES as the first endocrine disrupting chemical (EDC). Vaginal clear cell adenocarcinoma (CCAC), the most severe consequence of prenatal exposure to DES, affected only 0.1% of exposed females, while the far more prevalent teratogenic and reproductive effects of DES were only discovered when DES daughter were screened for CCAC. Initial studies, conducted before most DES daughters had tried to conceive, examined vaginal cancer and vaginal, cervical and uterine abnormalities. Subsequently, several controlled studies demonstrated the increased risk of adverse reproductive outcomes in DES daughters. While most DES daughters can eventually experience a live birth, this is less likely in women with genital tract abnormalities, in whom there is a two-thirds chance that each pregnancy will be unsuccessful. In DES sons, who have been far less studied, results suggest male reproductive toxicity, but are less consistent. The importance of dose and gestational age at initial exposure are discussed, and the implications of DES findings for the evaluation of risks from current EDCs emphasized.

Abnormalities, Drug-Induced↗
PubMed1976

Bone marrow metastases from prostatic cancer-marked cytolytic effect after only a few days of treatment with diethylstilbestrol.

A 42-year-old male patient became hospitalized with severe back pain and marked bleeding tendency from disseminated intravascular coagulation. The bone marrow aspirate showed numerous nests of cancer cells presumably from a prostatic carcinoma. After only 4 days of treatment with diethylstilbestrol his condition was markedly improved, and a new bone marrow aspirate showed extensive necrosis of the cancer cells.

Adult↗
PubMed1992

Chemiexcitation in the peroxidative metabolism of diethylstilbestrol. Metabolic products.

In the presence of the surfactant hexadecyltrimethyl ammonium bromide (CTAB) a cascade of electronically excited states accompanies the successive steps in the peroxidative metabolization of the strong estrogenic and tumourogenic diethylstilbestrol. Reversing the order by necessity, we report in this first paper results with the metabolites. Exposure of 4-hydroxypropiophenone, Z,Z-dienestrol or E,E-dienestrol to horseradish peroxidase and H2O2 promotes oxygen uptake and spectral alterations. Light emission is observed provided that the surfactant CTAB is present. With the three substrates, 4-hydroxybenzoic acid and a new metabolite, p-benzoquinone, have been identified. With both dienestrol isomers, 1-(4'-hydroxyphenyl)-propan-1-on-2-ol has been identified. In all cases the emission spectrum indicates the presence of several emitters. Possible chemiexcitation routes are pointed out. From the dramatic increase of the emission by enhancers, values as high as 1 x 10(-5) are inferred for the product of the quantum yields of chemiexcitation and energy transfer.

Dienestrol↗
PubMed2004

Agonist-induced internalization of leukotriene B(4) receptor 1 requires G-protein-coupled receptor kinase 2 but not arrestins.

The leukotriene B(4) (LTB(4)) receptor (BLT1) becomes desensitized upon repeated agonist stimulation. Little is known, however, about BLT1 internalization, which follows desensitization in most G-protein-coupled receptors (GPCR). In the current study, transiently expressed BLT1 readily internalized, after LTB(4) stimulation, in RBL-2H3 cells that express high levels of endogenous GPCR kinase 2 (GRK2) but did not in COS-7 or human embryonic kidney (HEK) 293 cells, which do not overexpress GRK. The internalization of BLT1 could be blocked in RBL-2H3 cells by coexpressing dominant-negative (DN) GRK2 K220R and could be promoted in HEK293 cells by coexpressing wild-type (WT) GRK2. Coexpression of WT or DN nonvisual arrestins had no effect on BLT1 internalization. Moreover, upon stimulation with LTB(4), BLT1 did not induce arrestin-green fluorescence protein redistribution in either cell type, even in the presence of overexpressed GRK2. Coimmunoprecipitation experiments confirmed that BLT1 could associate with GRK2 but not with arrestins. A C-tail-truncated mutant of BLT1 lost the capacity to internalize and associate with GRK2 upon exposure to LTB(4), suggesting that the C-tail was required for receptor internalization and association with GRK2. Taken together, our results indicate that the C terminus of BLT1 plays a pivotal role in receptor internalization and GRK2 association. Moreover, ligand-induced BLT1 internalization is dependent on GRK2 but independent of arrestins. This may allow differential, cell-type-specific signaling in response to LTB(4), depending on GRK expression levels.

Animals↗
PubMed1975

Reproductive tract lesions in male mice exposed prenatally to diethylstilbestrol.

Sixty percent of the male offspring from pregnant mice treated with diethylstilbestrol during gestation were sterile. The affected animals had gonadal changes which included intra-abdominal or fibrotic testes, or both. Additionally, nodular masses in the ampullary region of the reproductive tract were observed in 6 of 24 animals; one of these appeared to be preneoplastic.

Abnormalities, Drug-Induced↗
PubMed1977

Carbon-14-labeled diethylstilbestrol synthesis by the McMurry method: concurrent formation of hexestrol.

Isotopically labeled diethylstilbestrol prepared from p-methoxypropiophenone by coupling with TiCl3-LiA1H4 contained approximately 50% hexestrol. Nonlabeled preparations and a subsequent labeled preparation had less than 2% hexestrol in them. Initial examinations for purity by gas-liquid chromatography, thin-layer chromatography, and isotope dilution did not show the presence of hexestrol. Specific ion monitoring of a gas chromatography-mass spectrometry determination revealed the presence of the deithylstilbestrol-hexestrol mixture.

Carbon Radioisotopes↗
PubMed1970

Action of diethylstilbestrol on staphylococci: further observations on the effect of resting cells.

Diethylstilbestrol (DS) has been shown to be active against staphylococci and other gram-positive bacteria but not against gram-negative microorganisms. The present study extends these findings. Standardized suspensions of (14)C-labeled Staphylococcus aureus serotypes III and IV and Shigella flexneri were prepared and exposed to pharmacological concentrations of DS (1 to 20 mug/ml) under diverse environmental conditions; the cells were removed by membrane filtration and the presence of radioactive substances in release to the supernatant fraction was followed by standard radioisotopic techniques. Controls were exposed similarly to the hormone vehicle alone (buffer containing 2% ethyl alcohol). DS at bactericidal concentrations above 6 mug/ml caused significant leakage of cellular radioactivity of S. aureus labeled with (14)C-glucose and (14)C-glutamic acid within 1 to 4 hr after exposure to DS. Maximum leakage of radioactivity occurred under anaerobic conditions at 37 C. Absorption studies of (14)C-labeled DS indicated that the affinity of S. flexneri for DS is markedly less than that of S. aureus. This might be one reason for the resistance of gram-negative bacteria to DS.

Absorption↗
PubMed1996

Immunohistochemical method for detecting lesions in the prostate gland of bulls treated with diethylstilbestrol-dipropionate.

Hyperplastic and metaplastic lesions in the prostate gland of bulls are used as morphological evidence for the illegal administration of oestrogens or compounds with oestrogenic activity, like stilbenes. Exogenous and endogenous androgens can suppress the effects of these drugs, resulting in suspect or negative results. The detection of epithelial changes immunohistochemically with cytokeratin antibodies appeared to facilitate the diagnosis of hyperplasia and metaplasia in the prostate. A specific and sensitive method for detecting such lesions in formalin-fixed, paraffin-embedded prostate samples has been developed with the commercially available cytokeratin monoclonal antibody 34 beta E12, and applied to bulls treated with diethylstilbestrol-dipropionate. The highly reproducible staining pattern of 34 beta E12 can be used for the detection of hyperplasia and metaplasia in the prostate glands of animals treated illegally with oestrogens.

Animals↗
PubMed2004

Lectin binding patterns in hyperplastic and metaplastic bullock prostate tissues after diethylstilbestrol administration.

Hyperplasia and squamous metaplasia of the prostatic epithelium are conditions induced by oestrogens. Diethylstilbestrol (DES) has been banned from cattle used for beef production because of the health risks. The potential use of molecular markers for the detection of illegal oestrogen administration was evaluated by taking samples of prostatic tissue from control bullocks, bullocks which had been treated with oestrogens, and bullocks sacrificed 21 and 90 days after a single dose of DES. The expression of the glycoconjugates was examined by lectinhistochemistry and the lectin binding pattern was characterised in epithelium and connective tissue. In the animals sacrificed after 21 days there was an increase in the binding of one lectin (JAC) and there was an increase in the binding of one of the other lectins (DBA) in the animals sacrificed after 90 days. An increase in SWGA lectin staining was observed in the bullocks that had probably been treated with oestrogen and in the animals sacrificed 90 days after the inoculation with DES. There were also differences between the binding of SWGA in the control bullocks and the other groups.

Animals↗
PubMed2006

Prenatal diethylstilbestrol exposure and risk of breast cancer.

It has been hypothesized that breast cancer risk is influenced by prenatal hormone levels. Diethylstilbestrol (DES), a synthetic estrogen, was widely used by pregnant women in the 1950s and 1960s. Women who took the drug have an increased risk of breast cancer, but whether risk is also increased in the daughters who were exposed in utero is less clear. We assessed the relation of prenatal DES exposure to risk of breast cancer in a cohort of DES-exposed and unexposed women followed since the 1970s by mailed questionnaires. Eighty percent of both exposed and unexposed women completed the most recent questionnaire. Self-reports of breast cancer were confirmed by pathology reports. Cox proportional hazards regression was used to compute incidence rate ratios (IRR) for prenatal DES exposure relative to no exposure. During follow-up, 102 incident cases of invasive breast cancer occurred, with 76 among DES-exposed women (98,591 person-years) and 26 among unexposed women (35,046 person-years). The overall age-adjusted IRR was 1.40 [95% confidence interval (95% CI), 0.89-2.22]. For breast cancer occurring at ages >or=40 years, the IRR was 1.91 (95% CI, 1.09-3.33) and for cancers occurring at ages >or=50 years, it was 3.00 (95% CI, 1.01-8.98). Control for calendar year, parity, age at first birth, and other factors did not alter the results. These results, from the first prospective study on the subject, suggest that women with prenatal exposure to DES have an increased risk of breast cancer after age 40 years. The findings support the hypothesis that prenatal hormone levels influence breast cancer risk.

Adult↗
PubMed2000

Sexual dimorphism in diethylstilbestrol-induced prolactin pituitary tumors in F344 rats.

Female F344 rats treated chronically with diethylstilbestrol (DES) develop prolactin (PRL)-producing pituitary tumors. These tumors are larger in female than in male rats. To investigate gender differences in DES-induced pituitary tumor formation, we employed female and male rats and neonatally androgenized females, which received 100 microg of testosterone propionate (TP) after birth. At 3 months of age, all rats were deprived of their gonads and divided into control and DES-treated groups. Forty days after beginning treatment, control pituitary weight and serum PRL were similar in gonadectomized males (GDX), ovariectomized females (OVX) and androgenized-ovariectomized females (OVX + TP), but weight of DES-induced tumors was 2.5-fold higher and serum PRL 5.6-fold higher in OVX + DES than in GDX + DES or OXV + TP + DES (p<0.001). At the pituitary level, nuclear estrogen receptors (NE(2)R) amounted to >100 fmol/mg DNA in all rats receiving DES. However, NE(2)R were lower in OVX + DES (101.3+/-9.0 fmol/mg DNA) than in GDX + DES (174.6 +/-16.8; p<0.05) and in OXV + DES + TP (150.3+/-27.7; p<0.05). A similar profile was found for cytosolic progestin receptors. Using electron microscopy (EM), hyperplasia/hypertrophy of lactotropes was found in all DES-stimulated pituitaries. However, tumors of OVX + DES rats were enriched in hyperstimulated typical lactotropes, i.e., cells with high rate of hormonal synthesis, processing and secretion. Instead, tumors from GDX + DES and OVX + TP + DES rats were a mixture of typical and atypical lactotropes, i.e. a cell subpopulation with refractory secretory response and a few gonadotropes. In agreement with these data, immunoreactive pituitary PRL was lower in OVX + DES than in OVX + TP + DES and GDX + DES groups. Thus, differences in the sensitivity to DES, serum and tumor PRL, NE(2)R and progestin receptors between estrogenized female rats on one side and male and TP-androgenized females on the other, may by due in part to heterogeneity of cell populations. Our data further suggest that neonatal hypothalamic exposure to androgens, as in normal males or androgenized females with masculinization of hypothalamic centers, may condition the response to DES stimulation later in life.

Animals↗
PubMed1976

Possible role of dopamine in diethylstilbestrol-elicited accumulation of cyclic AMP in incubated male rat hypothalamus.

Pimozide and haloperidol, the dopaminergic antagonists, have been shown to effectively block diethylstilbestrol (DES)-elicited [3H] adenosine 3', 5'-monophosphate (cAMP) accumulation in incubated hypothalami from immature male rats. Several noradrenergic antagonists (i.e. propranolol, MJ-1999 and phenoxybenzamine) failed to reduce [3H]cAMP levels significantly. Pimozide was found to be more specific than haloperidol as it did not effect norepinephrine (NE)-elicited formation of [3H]cAMP, while the latter blocker caused a 48% reduction of the stimulation by NE. Pimozide was also more potent than haloperidol in inhibiting DES-stimulated [3H]cAMP formation. It can be inferred from these data that as a result of DES-receptor interaction dopamine (DA) is released and in turn activates DA-sensitive adenylate cyclase in the hypothalamus.

Animals↗
PubMed1985

Dopaminergic modulation of the diethylstilbestrol-induced proliferation of the anterior pituitary gland of the Fisher 344 rat.

Bromocriptine (CB 154), a potent agonist upon the D-2 receptor, blocks the proliferation of the mammotrophs and the elevation of serum prolactin concentration induced by chronic exposure of male Fisher 344 rats to diethylstilbestrol (DES). Fluphenazine, a dopamine receptor antagonist, blocks these effects of CB 154. We conclude that a D-2 receptor occurs on the proliferating mammotroph of the male Fisher 344 rat and that stimulation of this receptor inhibits prolactin release and stops the DES-induced proliferation of these cells.

Animals↗
PubMed1989

Prolonged neuroendocrine effects of a brief exposure of adult male rats to diethylstilbestrol.

Eleven weeks of exposure to diethylstilbestrol (DES) releasing capsules caused marked changes in neuroendocrine function in male rats sacrificed 22 months later. Plasma prolactin levels were increased and plasma LH levels were decreased in the DES-exposed as compared to the control animals. DES-treated animals had significantly decreased levels of dopamine (DA) in the median eminence and lower rates of DOPA accumulation after blockade of aromatic amino acid decarboxylase than did the control animals. Norepinephrine and serotonin content and 5-hydroxytryptophan content in the ME, the medial basal and the anterior hypothalamus were not significantly affected by DES treatment. Basal prolactin release in vitro was reduced in the DES animals while prolactin responsiveness to inhibitory effects of 10(-7) M DA was enhanced. From these data it appears that a relatively brief exposure to DES in early adulthood causes marked and persistent changes in tuberoinfundibular DA function that are responsible for continued hyperprolactinemia. Associated reductions in LH secretion also appear to be due to hypothalamic as opposed to pituitary factors.

Animals↗
PubMed1993

Long-term testosterone or diethylstilbestrol treatment affects gamma-aminobutyric acid and central-type benzodiazepine receptors but not peripheral-type benzodiazepine receptors in the female rat brain.

Steroids have often been associated with modulation of the GABAergic system in the central nervous system, mainly in ovariectomized rats. In the present study, the effect of the synthetic estrogen diethylstilbestrol (DES) and testosterone (T) on the density of peripheral and central benzodiazepine (BZ) and gamma-aminobutyric acid (GABAA) receptors was evaluated in the frontoparietal cortex and whole cerebellum of female rats during the peripubertal period. The density of peripheral-type BZ receptors was not altered in either of these organs, whether or not treated with DES or T. The density of central BZ and GABAA receptors in either frontoparietal cortex or whole cerebellum was significantly reduced following treatment with DES or T; however, the effect of DES was much more pronounced. The similarity of the effect of T to that of DES may suggest that the effect of T is mediated at least partially by intraovarian biosynthesis of estradiol-17 beta from the exogenously administered T. Collectively, these results may suggest that in female rats during the peripubertal period, sex steroids produce a down-regulatory effect on expression of the brain GABAA/BZ complex, in contrast to their well-established up-regulatory effect in adult ovariectomized rats.

Animals↗
PubMed1996

Antagonism by progesterone of diethylstilbestrol-induced pituitary tumorigenesis in Fischer 344 rats: effects on sex steroid receptors and tyrosine hydroxylase mRNA.

It is known that chronic exposure of F344 rats to diethylstilbestrol (DES) induces prolactin (PRL)-secreting pituitary tumors composed of proliferating mammotropic cells. In the present work, we studied the effects of progesterone (P4) on several parameters stimulated in the pituitary tumors (DES-T), such as nuclear estrogen receptors (NE2R), cytosolic progestin receptors (CP4R) and serum PRL. Additionally, we have measured in hypothalamus the mRNA levels for tyrosine hydroxylase (TH), the rate-limiting enzyme for synthesis of dopamine, the main PRL-inhibitory factor. We found that pellet implantation of P4 during 1 month significantly reduced weight, ligand binding to NE2R and CP4R and serum PRL in the tumorous glands. Reductions in sex steroid receptor binding were due to changes in Bmax without changes in Kd, as observed after Scatchard plot analysis. Receptor binding data, therefore, suggests a pituitary site of action of P4. TH mRNA expression was studied in tuberoinfundibular dopaminergic (TIDA) neurons by in situ hybridization techniques employing a 35S-labeled oligonucleotide probe. Mean number of grains/cell decreased significantly in DES-T, an effect partly reversed by P4 treatment. Frequency histograms were constructed by plotting the number of cells versus the number of grains/cell and examined by x2 test and analysis of residuals. We found that DES-T presented significantly more cells with less grains whereas in control glands, P4-treated rats and DES-T receiving P4, cells with a higher grain number prevailed. These results suggest that in addition to a direct pituitary effect, P4 may also antagonize DES-induced tumorigenesis acting on mRNA for TH and presumably on the activity of TIDA neurons of the hypothalamus. The use of DES-T as a model for hyperprolactinemia may allow further assessment of P4 effects in pituitary adenomas in humans.

Animals↗