Disease relevance of diethylstilbestrol

• Response differences between the strain and stock included the following: DES produced both pituitary tumors and mammary adenocarcinomas (MAC) in ACI rats only [1].
• The altered mitogen response should be a stimulus for a detailed analysis of the immune system in women exposed to DES during fetal life, some of whom develop later in life clear cell adenocarcinoma of the uterine cervix and vagina [2].
• The incidence of spontaneous and DES-induced cataracts in ER Delta 3 mice is 100%, yet these cataracts are absent from the wild-type mice [3].
• Animals given a combination of DES and EE showed tubular hyperplasia but not interstitial lesions; this finding was of particular interest because hamsters given this combination of estrogens do not develop gross renal tumors [4].
• Our data suggest that gene expression profiles of LNCaP human prostate cancer cells in response to PC-SPES are different from those found when diethylstilbestrol (DES), a synthetic estrogen, is used, suggesting that the estrogenic moieties within PC-SPES do not drive this expression signature [5].

Psychiatry related information on diethylstilbestrol

• The presence of elevated hippocampal ER levels during the perinatal critical period and evidence of functional transformation to the DNA binding state following DES treatment in vivo or estrogen incubation in vitro suggests that the hippocampus is a potential substrate for estrogen-mediated organizational events [6].

High impact information on diethylstilbestrol

• DES at 10(-7) M in the culture medium increased the number of sister chromatid exchanges (SCE); no further increases was obtained with higher concentrations of DES [7].
• Female mice from three inbred strains (BALB/cCrgl, C3H/Crgl, and C57BL/Crgl) and one noninbred stock [RU:NCS (RU)] were treated perinatally with estradiol benzoate (EB), diethylstilbestrol (DES), or sesame oil and were killed on postnatal days 30--36 [8].
• Neonatal DES treatment not only resulted in persistent changes in the cervicovaginal epithelium and in the hypothalamic-pituitary gland control system but also in the spleen lymphocyte mitogen response [2].
• After 17 days of DES treatment, the increase in prolactin synthesis in the hyperplastic pituitaries was not as marked as that in the tumors [9].
• However, while DES-induced pituitary growth exhibited quantitative, additive inheritance, the hemorrhagic phenotype exhibited recessive, epistatic inheritance [10].

Chemical compound and disease context of diethylstilbestrol

• Diethylstilbestrol (DES) treatment of weanling F344 female rats resulted in enlarged pituitary glands and diffuse pituitary prolactin (PRL) cell hyperplasia in all animals after 9 and 12 weeks of treatment [11].
• Hence, T substitution for 8 days at adulthood did not reverse infertility in rats treated neonatally with DES and provided evidence that infertility probably resulted from absence of cavernous spaces and/or accumulation of fat cells in the penis body [12].
• The synthetic estrogens, diethylstilbestrol (DES) and ethynylestradiol (EE2), are more potent than 17 beta-estradiol (E2) in inducing uterine weight gain in the neonatal rat, due to the binding of E2 to serum alpha-fetoprotein (AFP) [13].
• DES effects on glands appear related to continued hypertrophy of the luminal epithelium, from which uterine glands are derived [14].
• It appears that some other estrogenic compounds, such as bisphenol A and nonylphenol, may also follow a similar pattern of effects to DES, because we have recently shown that these compounds alter cell cycle kinetics, produce telomeric associations, and produce chromosomal aberrations [15].

Biological context of diethylstilbestrol

• We provide evidence that androgen response elements (ARE) II and III within the promoter region are responsible for the suppressive effects of DES and stimulatory effects of PC-SPES [5].
• This response to DES involved multilayering of basal epithelial cells, expression of cytokeratin 10, and up-regulation of the progesterone receptor [16].
• Cell-cycle analysis showed that the growth-inhibitory effect of DES, TAM or quercetin was due to a blocking effect in the G0-G1 phases [17].
• CD-1 pregnant female mice were injected with DES (100 micrograms/kg maternal BW) from days 9-15 of gestation [18].
• The relative binding affinity of quercetin, rutin, DES and TAM for type-II EBS correlated well with their potency as cell growth inhibitors [17].

Anatomical context of diethylstilbestrol

• The testis weights of BALB/c mice remained normal during DES treatment, whereas those of the C3H decreased with time [19].
• No significant differences were observed between the results obtained by the radioligand and enzyme immunoassay methods in the cytosol and nuclear fractions from the control and DES-treated tumors [20].
• In contrast, the prostates of alphaERKO mice exhibited no response to neonatal DES either immediately after exposure or throughout life up to 18 months of age [21].
• Uterus and liver served as positive and negative control tissues, respectively, for the effects of DES on IGF-I mRNA levels in OVX rats; mRNA levels were increased in uterus and decreased in liver after hormone treatment [22].
• The oviducts from the DES-withdrawn chicks and from aged nonlaying hens showed marked atrophy [23].

Associations of diethylstilbestrol with other chemical compounds

• Sprague-Dawley rats, resistant to estrogen-induced Leydig cell tumors, like C3H mice, also underwent testicular atrophy and lost LH receptors during DES treatment [19].
• In a separate experiment, administration of progesterone with DES decreased the concentration of nuclear ER to less than one-half that observed after administration of DES alone, with proportional decreases in both cytosolic and nuclear PgR [20].
• Sixteen previously untreated patients received DES (1 mg daily for 3 days) followed by FAC [5-fluorouracil (600 mg/m2): Adriamycin (50 mg/m2): Cytoxan (600 mg/m2)] i.v. on day 4 every 21 days [24].
• In the nine patients submitted to surgery after three DES plus FAC courses, the average thymidine labeling index and primer-dependent alpha-DNA polymerase labeling index were 27.8 and 73% of the pretreatment values [24].
• In spite of different structures and equilibrium parameters, E2, DES, and arachidonate are able to compete with each other for binding to the fetoprotein [25].

Gene context of diethylstilbestrol

• In contrast, we observe that Wnt7a mutant uteri display high levels of cell death in response to DES, whereas wild-type uteri display almost no cell death, revealing that Wnt7a plays a key role as a cell death suppressor [26].
• 4) Oestrogen (diethylstiboestrol-diphosphate, Honvan) after orchidectomy increased SHBG and hPr. n=6 [27].
• DES induced prostatic squamous metaplasia (SQM) in wt and betaERKO but not in alphaERKO mice, indicating an essential role for ERalpha, but not ERbeta, in the induction of SQM of prostatic epithelium [16].
• DES treatment also increased pituitary VIP content and VIP mRNA levels, but not in the hypothalamus and cerebral cortex [28].
• These findings clearly demonstrate cell-specific PR localization and region-specific effect of DES on PR in the developing rat Müllerian duct, and provide fundamental information critical for investigating the tissue-specific mechanisms underlying the prenatal response to estrogen receptor agonists [29].

Analytical, diagnostic and therapeutic context of diethylstilbestrol

• Proliferative activity on tumor biopsies was evaluated immediately before and after treatment with DES, 24 h after chemotherapy and, in nine patients, at the time of radical surgery [24].
• Use of an immunohistochemical method for the detection of ER in frozen sections indicated that the receptor was localized in the glandular epithelium in both control and DES-treated tumors [20].
• Prepubertal ovariectomy of the prenatally DES-treated animals could only partially reverse the effects observed in the skeleton of the DES-treated animals [18].
• The epithelial mitotic index was also 2-fold higher than control values 16-18 h after DES treatment [30].
• Four types of coculture were set up as follows: 1) Control testis with control MD; 2) DES-treated testis with DES-treated MD; 3) Control testis with DES-treated MD; 4) DES-treated testis with control MD [31].

References