- [Inhibitory effect of diethylstilbestrol on clinical strains of Candida albicans susceptible and resistant to azoles]. [Journal Article]
- RIRev Iberoam Micol 2019 Jul 09
- CONCLUSIONS: DES showed antifungal activity on all clinical C. albicans strains isolated from patients with dental and medical diseases. It showed the highest potency on the FLZ-resistant isolate.
- Rapid prolactin induction in adult male rats after treatment with diethylstilbestrol. [Journal Article]
- JNJ Neuroendocrinol 2019 Jul 08; :e12769
- Diethylstilbestrol (DES) is a synthetic estrogen known to disrupt the endocrine system and to cause reproductive toxicity mediated through the hypothalamic-pituitary-adrenal axis; however, its molecu…
Diethylstilbestrol (DES) is a synthetic estrogen known to disrupt the endocrine system and to cause reproductive toxicity mediated through the hypothalamic-pituitary-adrenal axis; however, its molecular mechanism of action is poorly understood. In this study, we gathered evidence that after only 1 week of exposure to DES, blood testosterone dramatically decreased and that this decrease is associated with strong induction of prolactin (PRL). Even with the increase in PRL, the luteinizing hormone and follicle stimulating hormone mRNAs slightly decreased. Our results show that after 48 h of a single dose of DES, there was a six-fold increase in PRL expression. After exploring the upstream mechanisms, we determined that dopamine, which inhibits PRL secretion in male rats, did not decrease in the pituitary gland of DES-treated rats; whereas, vasoactive intestinal peptide (VIP), which mediates the acute release of PRL, was elevated. Serotonin (5-HT) increased in the brain of male rats 24 h after a single DES treatment; however, PRL, VIP, or 5-HT were not induced by DES in female rats. Our results indicate that DES induces the expression of pituitary PRL in male rats by stimulating VIP in the hypothalamus and 5-HT in the central nervous system. This article is protected by copyright. All rights reserved.
- Diethylstilbestrol Alters the Expression of Activins in the Neonatal Mouse Ovary In Vitro. [Journal Article]
- VIn Vivo 2019 Jul-Aug; 33(4):1095-1102
- CONCLUSIONS: Alterations in activin signaling are involved in the polyovular follicle induction by DES.
- Prenatal Diethylstilbestrol Exposure and Risk of Depression in Women and Men. [Journal Article]
- EEpidemiology 2019 Jun 25
- CONCLUSIONS: Prenatal DES exposure was not associated overall with risk of depression in women or men. In women, exposure in early gestation or to a low cumulative dose may be weakly associated with an increased depression risk.
- Diethylstilbestrol in the Treatment of Castration-resistant Prostate Cancer: A Lower-middle-income Country Experience. [Journal Article]
- CCureus 2019 Apr 16; 11(4):e4470
- CONCLUSIONS: DES is an effective, economical, and relatively safe drug in patients with CRPC.
- Diethylstilbestrol inhibits human and rat 11β-hydroxysteroid dehydrogenase 2. [Journal Article]
- ECEndocr Connect 2019 Jun 01
- Glucocorticoid hormone might cause intrauterine growth restriction. The glucocorticoid metabolizing enzyme 11β-hydroxysteroid dehydrogenase 2 (HSD11B2) in the placenta eliminates excess levels of glu…
Glucocorticoid hormone might cause intrauterine growth restriction. The glucocorticoid metabolizing enzyme 11β-hydroxysteroid dehydrogenase 2 (HSD11B2) in the placenta eliminates excess levels of glucocorticoids during pregnancy. The aim of the current study was to define the effects of diethylstilbestrol (DES) on HSD11B2 activity in the mammalian placentas and identify its mode of action. Rat and human placental microsomal HSD11B2 were incubated with different concentrations of DES and IC50 values were determined. The mode of action was analyzed by incubation of DES together with substrates, glucocorticoid and NAD+. DES suppressed rat and human HSD11B2 with IC50 values of 5.33 and 12.62 μM, respectively. DES was a competitive inhibitor of rat and human HSD11B2 when steroid substrates were added, while it was an uncompetitive inhibitor when cofactor NAD+ was exposed. Oral administration of DES (0.5 mg/kg) to the rat delayed the cortisol metabolism in adult female Sprague-Dawley rats, as indicated by the increases in cortisol's elimination half-life, maximum concentration, and AUC. In conclusion, DES is a potent HSD11B2 inhibitor, possibly contributing to the intrauterine growth restriction.
- Transcriptomic points-of-departure from short-term exposure studies are protective of chronic effects for fish exposed to estrogenic chemicals. [Journal Article]
- TAToxicol Appl Pharmacol 2019 Jun 19; 378:114634
- Resource limitations often require risk assessors to extrapolate chronic toxicity from acute tests using assessment factors. Transcriptomic dose-response analysis following short-term exposures may p…
Resource limitations often require risk assessors to extrapolate chronic toxicity from acute tests using assessment factors. Transcriptomic dose-response analysis following short-term exposures may provide a more reliable and biologically-based alternative for estimating chronic toxicity. Here, we demonstrate that transcriptomic dose-response analysis in fish following short-term exposure to endocrine disrupting chemicals (EDCs) provides estimates of chronic toxicity that may be used as protective points-of-departure (POD) for risk assessment. The benchmark dose (BMD) method was used on publicly available datasets (n = 5) to determine transcriptomic PODs in fish exposed to three EDCs (bisphenol A, ethinylestradiol, and diethylstilbestrol). To test for potential bias related to data processing, our analysis compared the effect of different normalization, filtering, and BMD-grouping methods on the transcriptomic PODs. The resulting PODs were then compared to the empirically-derived chronic LOEC of each substance. Normalization and filtering methods had limited impact on the final PODs. However, we found that PODs derived from ontology- or pathway-based gene grouping methods were highly variable, whereas PODs from grouping methods that focused on the most responsive genes were more stable and provided POD estimates that were most similar to the chronic LOEC. Overall, 72% of transcriptomic PODs were within 1 order of magnitude of the chronic LOEC, regardless of data analysis method. When our recommended analysis approach was applied, the concordance improved to 100%. These results suggest that toxicogenomic dose-response analysis has the potential to be a protective decision-support tool for compounds with chronic toxicity, such as EDCs.
- Pro-Apoptotic Effects of Estetrol on Long-Term Estrogen-Deprived Breast Cancer Cells and at Low Doses on Hormone-Sensitive Cells. [Journal Article]
- BCBreast Cancer (Auckl) 2019; 13:1178223419844198
- CONCLUSIONS: The pro-apoptotic effects of E4 and E3 on LTED cells and at low doses on MCF-7 cells indicate that these steroids could be used as therapeutic agents for endocrine-resistant or sensitive breast cancer.
- Determination of twenty pharmaceutical contaminants in soil using ultrasound-assisted extraction with gas chromatography-mass spectrometric detection. [Journal Article]
- CChemosphere 2019; 232:232-242
- In this paper, an analytical method for the simultaneous determination of twenty pharmaceuticals (eight non-steroidal anti-inflammatory drugs, five oestrogenic hormones, two antiepileptic drugs, two …
In this paper, an analytical method for the simultaneous determination of twenty pharmaceuticals (eight non-steroidal anti-inflammatory drugs, five oestrogenic hormones, two antiepileptic drugs, two β-blockers, and three antidepressants) in soils was developed. The optimal method included ultrasound-assisted extraction, a clean-up step on a silica gel column, derivatization using N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) and 1% trimethylchlorosilane (TMCS) in pyridine and ethyl acetate (2:1:1, v/v/v) for 30 min at 60 °C, and determination by gas chromatography-mass spectrometry working in the selected ion monitoring mode. This affords good resolution, high sensitivity and reproducibility, and freedom from interferences even from complex matrices such as soils. The method detection limits ranged from 0.3 to 1.7 ng g-1, the intra-day precision represented as RSDs ranged from 1.1 to 10.0%, and the intra-day accuracy from 81.3 to 119.7%. The absolute recoveries of the target compounds were above 80%, except for valproic acid and diethylstilbestrol. The developed method was successfully applied in the analysis of the target compounds in soils collected in Poland. Among the 20 pharmaceuticals, 12 compounds were detected at least once in the soils. The determination of antiepileptic drugs, β-blockers, and antidepressants was also performed for the first time.
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- Mice lacking membrane estrogen receptor 1 are protected from reproductive pathologies resulting from developmental estrogen exposure. [Journal Article]
- BRBiol Reprod 2019 May 29
- Both membrane and nuclear fractions of estrogen receptor 1 (ESR1) mediate 17β-estradiol (E2) actions. Mice expressing nuclear (n)ESR1 but lacking membrane (m)ESR1 (nuclear-only estrogen receptor 1 [N…
Both membrane and nuclear fractions of estrogen receptor 1 (ESR1) mediate 17β-estradiol (E2) actions. Mice expressing nuclear (n)ESR1 but lacking membrane (m)ESR1 (nuclear-only estrogen receptor 1 [NOER] mice) show reduced E2 responsivity and reproductive abnormalities culminating in adult male and female infertility. Using this model, we investigated whether reproductive pathologies caused by the synthetic estrogen diethylstilbestrol (DES) are mitigated by mESR1 ablation. Homozygous and heterozygous wild-type (WT and HET, respectively) and NOER male and female mice were subcutaneously injected with DES (1 μg/g body weight [BW]) or vehicle daily from postnatal day (PND) 1-5. Uterine histology was assessed in select DES-treated females at PND 5, whereas others were ovariectomized at PND 60 and treated with E2 (10 ng/g BW) or vehicle 2 weeks later. Neonatal DES exposure resulted in ovary-independent epithelial proliferation in the vagina and uterus of WT but not NOER females. Neonatal DES treatment also induced ovary-independent adult expression of classical E2-induced transcripts (e.g. Ltf, Ezh2) in WT but not NOER mice. Males were examined around PND 90. DES-treated WT and HET males showed smaller testes and a high incidence of bacterial pyogranulomatous inflammation encompassing the testes, epididymis and occasionally the ductus deferens with spread to lumbar lymph nodes; such changes were largely absent in NOER males. Results indicate that male and female NOER mice are protected from deleterious effects of neonatal DES and thus, mESR1 signaling is required for adult manifestation of DES-induced reproductive pathologies in both sexes.