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 883 records · Page 49Linked to original sources
PubMedDate not supplied

Does diethylstilbestrol (DES) change the stress fiber organization in C6 rat glioma cells?

C6 Rat glioma cells acquire an astrocyte-like morphology (cytoplasmic shrinking) after exposure to beta-adrenergic compounds (e.g., isoproterenol) in serum-free medium. This morphological response is mediated by elevation of the intracellular cAMP level and possibly by activation of a kinase phosphorylating and inactivating the myosin-L-kinase in analogy to observations with smooth muscle cells. The result is a disturbance of the stress fiber function, which depends on a cooperation between actin and myosin. Diethylstilbestrol (DES) induces an identical morphological response in these cells under serum-free conditions. However, under the influence of DES no increase of the cAMP level was observed. In addition, at concentrations not inducing these morphological responses, DES inhibits the isoproterenol-induced effect when administered simultaneously or prior to the beta-receptor agonist. DES does not inhibit the isoproterenol-mediated morphological response when added after isoproterenol treatment. Furthermore, if serum is added to cells showing the isoproterenol- or DES-mediated astrocyte-like morphology (DES or isoproterenol present all the time) the cells regain their normal fibroblast-like morphology within 30 min. In view of these results the question arises whether DES interferes with myosin-L-chain phosphorylation or whether it directly interacts with the cytoskeleton stress fiber components, as cytochalasin B1 does. Thus it remains to be established whether the observed effects are related to the estrogenic activity of DES. Similar effects were observed with Syrian hamster embryo fibroblasts under the influence of DES and the naturally occurring steroid estrogen 17-beta-estradiol.

Animals↗
PubMed1986

Diethylstilbestrol. A novel F0-directed probe of the mitochondrial proton ATPase.

At low concentrations, diethylstilbestrol (DES) is shown to be a potent F0-directed inhibitor of the F0F1-ATPase of rat liver mitochondria. In analogy to other F0-directed inhibitors, DES inhibits both the ATPase and ATP-dependent proton-translocation activities of the purified and membrane bound enzyme. When added at low concentrations with dicyclohexylcarbodiimide (DCCD), a covalent inhibitor, DES acts synergistically to inhibit ATPase activity of the complex. At higher concentrations, DES restores DCCD-inhibited ATPase activity. However, there is no restoration of ATP-dependent proton translocation. Under these conditions DCCD remains covalently bound to the F0F1-ATPase complex and F1 remains bound to Fo. Significantly, when the F0F1-ATPase is inhibited by the Fo-directed inhibitor venturicidin rather than DCCD, DES is also able to restore ATPase activity. In contrast, DES is unable to restore ATPase activity to F0F1 preparations inhibited by the Fo-directed inhibitors oligomycin or tricyclohexyltin. However, combinations of [DES + DCCD] or [DES + venturicidin] can restore ATPase activity to F0F1 preparations inhibited by either oligomycin or tricyclohexyltin. Results presented here indicate that the F0 moiety of the rat liver mitochondrial proton ATPase contains a distinct binding site for DES. In addition, they suggest that at saturating concentrations simultaneous occupancy of the DES binding site and sites for either DCCD or venturicidin promote "uncoupled" ATP hydrolysis.

Animals↗
PubMed1989

Diethylstilbestrol metabolites and analogs. Stereochemical probes for the estrogen receptor binding site.

Indenestrol A (IA) and indenestrol B (IB) are analogs and metabolites of diethylstilbestrol (DES). These compounds have high binding affinity with the estrogen receptor (ER) but possess weak uterotropic activity. Due to their chemical structures, IA and IB exist as mixtures of enantiomers. We investigated whether the poor biological activity of these compounds was due to differential activity of the enantiomers. We also utilized these compounds as probes to determine the extent of stereochemical sensitivity in the ER ligand binding site. The IA and IB enantiomers were separated to greater than 98% purity using a chiral high pressure liquid chromatography column. Their enantiomeric nature was confirmed by mass spectrometry and NMR. The purified IA enantiomer peak 1 was derivatized with 4-bromobenzoyl chloride. The resulting di(4-bronobenzoate) IA was analyzed by x-ray crystallography and the absolute enantiomeric conformation assigned is C(3)-R. The IA enantiomers designated IA-R and A-S were assayed by competitive binding to cytosolic ER. The competitive binding index was estradiol, 100; DES, 286; IA-Rac (racemic mixture of IA), 143; IA-R, 3; and IA-S, 285; the index showed that ER demonstrates a stereochemical chiral preference. The IB enantiomers did not show a binding preference: IB, 145; IB-1, 100; and IB-2, 143. The differences in the IA enantiomer binding were shown to be due to competitive interactions by Lineweaver-Burk analysis of saturation binding of estradiol to ER in the presence of 1-, 5-, and 10-fold molar excess of competitor. Differences in binding affinity of the enantiomers could be partially explained by differences in the association rate constant (k+1) determined by association rate inhibition studies in which IA-S was 15 times more active than IA-R. Nuclear estrogen receptor levels were measured 1 h after in vivo treatment with doses of 5-20 micrograms/kg. The IA-Rac produced only 60% of the levels is compared with DES. Nuclear ER levels were checked every 30 min up to 2 h with no apparent difference, indicating that the low early levels were not due to a delayed estrogen receptor retention. When the enantiomers were tested individually only a dose of 10 micrograms/kg IA-S translocated ER to a level comparable to DES, while IA-R showed low levels at several doses. These results suggest that the poor biological activity of IA may be related to the differential ER interaction of its enantiomers.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Influence of age on induction of mammary tumors by diethylstilbestrol in C3H/HeN mice with low murine mammary tumor virus titer.

C3H/HeN female mice with low murine mammary tumor virus titer (MTV-) were fed diets containing a targeted concentration of 640 ppb diethylstilbestrol [(DES) CAS: 56-53-1; 4,4'-(1,2-diethyl-1,2-ethenediyl)bis-phenol]. Mice were started on DES at 3, 5, 7, or 9 weeks of age. Some continued on the diet throughout the rest of their life-spans, whereas others were killed as soon as they had been fed DES for 2, 4, 6, 8, 10, or 12 weeks. Controls were also examined throughout the study. Among mice killed early, the only observation significantly influenced by age at the start of DES treatment was the presence or absence of corpora lutea (CL). DES did not prevent CL from appearing in mice started on DES at 7 or 9 weeks of age, but it did prevent their appearance in about 25% of the mice started at 5 weeks and in up to 75% of the mice started at 3 weeks of age. In the life-span-exposure groups, CL either disappeared or were never formed in 88% or more of the mice, regardless of age at the start of treatment. Neoplastic or presumptive preneoplastic lesions apparently influenced by DES in the life-span-treatment groups included ovarian tubular adenomas; granulosa cell tumors and luteomas; pituitary cystoid degeneration, hyperplasia, and adenomas; uterine adenocarcinomas and cervical adenosis; mesotheliomas; and mammary hyperplastic alveolar nodules (HANs) and adenocarcinomas. Luteoma and granulosa cell tumor incidences were reduced by DES, regardless of age at the start of treatment. Influence of age at the start of treatment was minimal or not apparent for mesotheliomas, uterine adenocarcinomas, or pituitary adenomas; however, pituitary cystoid degeneration and hyperplasia and cervical adenosis occurred in higher frequency and/or with shorter duration of DES exposure the earlier that treatment was started. A delay in the start of DES treatment was associated with a remarkable delay in HAN and mammary adenocarcinoma development. This was especially apparent in young mice (3-7 wk old) in which a 2-week delay in treatment resulted in a 20-week delay in HAN or tumor onset. Age at the start of treatment was a major factor in susceptibility of C3H/HeN-MTV- female mice to DES-induced mammary tumorigenesis.

Adenocarcinoma↗
PubMed1986

Influence of neonatal steroid (diethylstilbestrol, allylestrenol) treatment on the sexual behaviour of the adult rat.

A single neonatal treatment with diethylstilbestrol (DES) or allylestrenol (AE) considerably depressed the sexual activity of male rats in adulthood. DES had a stronger depressive effect than AE. Though the adult sexual activity of intact female rats was also reduced by DES it was not influenced by AE. Ovariectomized females that had been hormone-treated before experimental mating showed reduced sexual activity under the influence of neonatal DES-treatment but increased sexual activity when treated neonatally with AE.

Allylestrenol↗
PubMed1986

Leuprolide versus diethylstilbestrol for previously untreated stage D2 prostate cancer. Results of a prospectively randomized trial.

In a randomized, prospective trial, 199 previously untreated patients with Stage D2 prostatic cancer were treated with 3 mg/day diethylstilbestrol (DES) or 1 mg/day leuprolide acetate, a luteinizing hormone releasing hormone analog. Both DES and leuprolide suppressed testosterone to the desired castrate levels. Objective measures of disease, such as acid phosphatase levels, and subjective measures, such as bone pain, performance status, and mobility, showed similar decreases in both groups. No progression of disease was seen in 86 per cent of the leuprolide-treated group, compared with 85 per cent of the DES-treated group. The time to disease progression, development of adverse reaction requiring discontinuation of treatment, or death was identical for the two groups. Hot flashes were more common with leuprolide than with DES. Gynecomastia and breast tenderness, nausea and vomiting, and peripheral edema occurred more often in the DES group. Of those taking DES, 13 per cent discontinued treatment because of side effects, compared with 3 per cent of those taking leuprolide.

Acid Phosphatase↗
PubMed1987

Induction of hepatic tumors by diethylstilbestrol in N-nitrosobutylurea-initiated female rats.

The carcinogenic effect of estrogens, diethylstilbestrol (DES) and 17 beta-estradiol (E2), and its modification by N-nitrosobutylurea (NBU) were studied in female W/Fu rats. Multiple mammary tumors (MT) of medullary carcinoma type developed at a high rate following prolonged treatment with estrogens. All MTs were located adjacent to the nipple and were slow-growing. The induction rate, multiplicity and size of estrogen-induced MTs were not influenced by pretreatment with a small amount of NBU, which alone did not induce any tumor. Ten of 12 rats (82%) receiving combined treatment with NBU and DES developed hepatic tumors (HT), while no rats in other treatment groups developed HT. All HTs were multiple nodules of various sizes bulging from the liver surface, and were considered to be neoplastic nodules. A high frequency of HT development was unexpected, because independent treatment with NBU or DES alone did not induce HT in female rats. It appears that DES played a role as a carcinogen, inducing MT and pituitary tumor (PT) through its estrogenic potency (like natural estrogen, E2), while it also acted as a promoter or co-carcinogen in the induction of HT through its pharmacologic effects. These findings may be relevant to an increased frequency of liver neoplasm among women taking oral contraceptives containing synthetic estrogens.

Animals↗
PubMed1986

Free histones in the cells of the rat uterus after neonatal treatment with diethylstilbestrol or allylestrenol.

Neonatal diethylstilbestrol and allylestrenol treatments resulted in a prompt release of free histones that could be demonstrated histochemically by the phosphomolybdic-acid-benzidine reaction. This effect could not be observed in the uterus of 6-10-week old rats but reappeared between 11-14 weeks in the myometrium and uterine epithelium without any repeated treatment. This may be due to the increased production of endogenous steroids. The finding suggest caution when applying steroids to pregnants and neonates.

Allylestrenol↗
PubMed1987

Effect of embryonic and/or neonatal diethylstilbestrol and allylestrenol treatment on postnatal development of the chick testis.

The synthetic steroid diethylstilbestrol (DES) and the steroid-like allylestrenol (AE) have been used for years in human medicine for the protection of pregnancy. The hazards to the fetus of gestational DES treatment are well established [2, 17, 18]. Knowledge of a similar effect of AE is still fragmentary. Therefore, further studies are required of the after-effects of embryonic and perinatal AE exposure. In our earlier experiments with polypeptide hormones [4, 5, 6] we have observed that perinatal age is a critical period in the maturation of hormone receptors. In this period the presence of hormone induces the development of its specific receptors. The phenomenon is termed hormonal imprinting [4, 5, 6]. During its maturation the receptor is flexible and the presence of non-specific hormones capable of binding to it may alter its normal development Accordingly, even a single hormone injection in the perinatal period may alter the hormone-sensitivity of the target organ.

Allylestrenol↗
PubMed1988

Hormonal imprinting and damages caused by fetal steroid treatment. Influence of fetal treatment with pregnancy-protecting steroids (allylestrenol, diethylstilbestrol) on the effect of gonadotropin administered to cockerels perinatally and at the age of six weeks.

Single fetal (9th day) treatment with either diethylstilbestrol (DES) or allylestrenol (AE) caused a considerable decrease, both at the age of five days and six weeks, in the weight of the testicles and the diameter of the seminiferous cords, while the ratio of spermatogonia to primary spermatocytes increased. When measured either at the age of five days or six weeks, gonadotropin treatment [a combination of follicle stimulating hormone (FSH) and luteinizing hormone (LH)], administered twice daily for three days after the hatching, led to an increase in the above-mentioned parameter and to a shift in the cell ratio towards the control value. However, the absolute value of the controls treated with FSH-LH was by far not reached. The effect of perinatal treatment could be detected even in adulthood, namely, at the age of five days the response capability was relatively weak in the cockerels treated with DES and AE, while high responsiveness was observed at the age of six weeks. In some cases the relative value of the increment exceeded even that of the control; however in absolute term it was well below the control. On the basis of these experiments it might be concluded that hormonal imprinting evoked by FSH-LH treatment also occurs in the gonad damaged by DES and AE. The setting in of imprinting ameliorates the damages caused by DES and AE and increases the response capability of the cells.

Allylestrenol↗
PubMed1988

Long-term effects of exposure to diethylstilbestrol.

In 1985 nearly 1,700 persons who had exposure to diethylstilbestrol (DES)--520 mothers, 1,079 daughters, and 94 sons--responded to a mailed questionnaire about their general health status. Results were compared with responses to the 1985 National Health Interview Survey and other population-based studies. As with research findings in animals, conditions that suggest possibly impaired immune function--that is, respiratory tract infections, asthma, arthritis, and lupus--were reported more frequently among the persons with DES exposure. Conditions that may involve altered endocrine function were also more frequent among such persons. Given the biased sample, findings from this preliminary survey are seen as guidelines to areas meriting more rigorous research.

Adolescent↗
PubMed1988

Megestrol acetate plus minidose diethylstilbestrol in the treatment of carcinoma of the prostate.

A multicenter randomized trial comparing megestrol acetate 120 mg/d, plus diethylstilbestrol (DES) 0.1 to 3 mg/d in patients with stage D2 prostate cancer was undertaken to compare the efficacy and toxicity of these two regimens. Pretreatment characteristics, including pathologic grade, performance status, age, and disease-related symptoms were similar in the two groups. Of 81 patients who have been entered in the study, 77 are evaluable for response and toxicity at a mean follow-up of 13.3 months. Using National Prostate Cancer Project (NPCP) criteria, no difference in response rate is noted (73% v 76%) or in disease-free survival and overall survival. The ability to suppress serum testosterone to castration levels and to maintain this suppression is equivalent in both treatment groups. However, treatment-related toxicity, including edema, hypertension, and gynecomastia, occurred at a significantly greater frequency, severity, and after a shorter treatment period in the DES-treated group. No difference in major cardiovascular events was noted. Since megestrol acetate plus minidose DES is equivalent to DES in achieving treatment responses in patients with carcinoma of the prostate, it is a preferable treatment because of its improved side-effect profile.

Aged↗
PubMed1988

Pregnancy after gamete intrafallopian transfer in a woman with primary infertility and in utero exposure to diethylstilbestrol. A case report.

In utero exposure to diethylstilbestrol (DES) has an adverse effect on reproductive performance and may be associated with infertility. Gamete intrafallopian transfer (GIFT) is a new reproductive technique that has been advocated as an alternative to in vitro fertilization in women with at least one normally functioning fallopian tube. The process involves the translaparoscopic placement of oocytes and sperm into the fallopian tube. The technique has been successful in treating infertility due to endometriosis, male factors and immunologic factors as well as unexplained infertility. We accomplished the first successful GIFT procedure in a woman with significant uterine effects from prenatal DES exposure. This technique may prove to be an effective treatment for infertile women with DES exposure who have no adequate explanation for their infertility.

Adult↗
PubMed1988

Role of metabolism and DNA adduct formation in the induction of sister chromatid exchanges in human lymphocytes by diethylstilbestrol.

Recent studies have shown that diethylstilbestrol (DES) induces sister chromatid exchanges (SCEs) in lymphocytes from pregnant and premenopausal women but has only a slight effect on lymphocytes from post-menopausal women or men. In this study blood specimens from premenopausal women were used to define the role of different metabolic pathways on DES-induced formation of SCEs and to determine whether conditions resulting in induction of SCEs also induced detectable levels of DNA adducts. Exposure of lymphocytes in vitro to 0-40 microM DES induced a concentration-dependent increase in SCEs. Addition of indomethacin to the cultures partially abolished DES-induced SCEs, suggesting involvement of prostaglandin synthetases in the formation of specific DES metabolites that cause SCEs. alpha-Naphthoflavone, an inhibitor of cytochrome P-450 monooxygenases, had no effect on DES-induced SCEs. Cells exposed to DES at doses sufficient to cause large increases in SCE induction did not have adducts detectable by a 32P-postlabeling assay capable of revealing adducts at a level of 1 adduct/10(9) normal nucleotides.

Benzoflavones↗
PubMed1988

Adverse outcomes of pregnancy in women exposed to diethylstilbestrol in utero.

We analyzed data collected by interview and medical record review for 200 women exposed to diethylstilbestrol (DES) and 12,240 unexposed women to evaluate the relation between maternal DES exposure and outcomes of pregnancy. Low birth weight, short gestation, bleeding in the first trimester, toxemia, breech presentation and premature rupture of the membranes occurred more often among the exposed women. These relationships remained statistically significant after the use of linear regression and logistic regression analyses to control for multiple confounding factors. Both exposed women and their physicians should be aware of the possible relationship between maternal exposure to DES and late adverse outcomes of pregnancy. Close medical supervision of these women throughout pregnancy and delivery is recommended.

Demography↗
PubMed1988

Growth inhibition by diethylstilbestrol and relapse of the Noble rat prostatic tumor.

The response of androgen-sensitive Noble (Nb) rat prostatic adenocarcinoma [2Pr-121D (1)] to varying doses (50 approximately 1,000 micrograms/kg body weight) of diethylstilbestrol (DES) was investigated and characterized with respect to cytosol and nuclear androgen binding profiles, histology and pattern of relapse. Inhibition of tumor growth was closely related to the dose of DES. Treatment at all but the lowest dose (50 micrograms/kg) initially caused tumor regression, whereas serum testosterone concentrations in all groups, including that receiving the lowest dose, were decreased to castrate levels. Histologically, while extensive cellular destruction was clearly evident at higher doses of DES, some active tumor cells appeared to survive. Tumors eventually relapsed when higher doses of DES were stopped or with the continued administration of low doses. The cytosol dihydrotestosterone (DHT) receptor in this tumor line, as determined by sucrose density gradient, dextran charcoal and Sephadex column methods, was negative. Nuclear binding, however, was positive. Salt-extractable and salt-resistant fractions of nuclei derived from the untreated primary tumor and relapsed tumor following DES treatment contained high affinity androgen receptor. Comparison of binding constants revealed no significant differences. Our findings, based on the Nb rat prostatic tumor model, indicate that DES acts not only by eliminating circulating testosterone, but also by a direct cytotoxic effect on malignant cells. The results also suggest the lack of an apparent relationship between the loss of hormone responsiveness associated with recurrence of prostatic tumor growth and nuclear androgen binding parameters.

Adenocarcinoma↗
PubMed1988

Cervical and vaginal cancer detection at a regional diethylstilbestrol (DES) screening clinic.

From 1979 to 1986, 500 women were enrolled in a New York State regional diethylstilbestrol (DES) clinic for the early detection of DES-associated adenocarcinoma of the cervix or vagina. Only 66 DES-exposed females were seen at Roswell Park Memorial Institute in the 6-year period prior to the establishment of the DES screening clinic. Most (40%) learned of the DES screening clinic through television public service announcements. Documentation by physician, pharmacy, or hospital records of intrauterine DES exposure was possible in only 15.2% of the cases. Because of a mean age of 24 years of the DES-exposed patients, most physician, pharmacy, and hospital records were not readily available from that time period. In 5.2% of the patients enrolled in the DES clinic, review documented that the mother had not taken DES or other synthetic estrogen analogs. Among the 474 evaluable DES patients, gross vaginal or cervical abnormalities were present in 13.5% and DES-associated adenosis was seen in 16.0%. Sixteen (3.4%) developed squamous dysplasia, one developed squamous in situ carcinoma of the cervix, and one developed invasive squamous cell carcinoma of the cervix. During the 6-year period of the DES screening clinic, no patient developed DES-associated adenocarcinoma of the cervix or vagina. The utility of such specialized clinics is discussed.

Adenocarcinoma↗