- Comments on prenatal diethylstilbestrol exposure and high-grade squamous cell neoplasia of the lower genital tract. [Letter]
- AJAm J Obstet Gynecol 2016 Sep 28
- Activation of G protein-coupled estrogen receptor 1 mimics, but does not mediate, the anti-proliferative action of estradiol on pituitary lactotrophs in primary culture. [Journal Article]
- EJEndocr J 2016 Oct 19
- Estrogen binds to nuclear estrogen receptors (ERs) to modulate transcription of target genes in estrogen-responsive cells. However, recent studies have shown that estrogen also binds to cytoplasmic m...
Estrogen binds to nuclear estrogen receptors (ERs) to modulate transcription of target genes in estrogen-responsive cells. However, recent studies have shown that estrogen also binds to cytoplasmic membrane ERs to modulate protein kinase signaling cascades, leading to non-genomic actions. We investigated whether either nuclear or membrane ERs, including G protein-coupled estrogen receptor 1 (Gper1), mediate the inhibitory action of estrogen on insulin-like growth factor-1 (IGF-1)-induced proliferation of pituitary lactotrophs in primary culture. The cytoplasmic membrane-impermeable bovine serum albumin-conjugated estradiol (BSA-E2) at 1 nM, an equimolar concentration at which 17β-estradiol (E2) exerts anti-proliferative effects, did not inhibit IGF-1-induced lactotroph proliferation. In contrast, diethylstilbestrol, which is known to selectively activate nuclear ERs but not membrane ERs, inhibited IGF-1-induced proliferation and modulated mRNA expression of estrogen-responsive genes to a similar degree as E2. Activation of Gper1 by its agonist G-1 inhibited IGF-1-induced proliferation in a dose-dependent manner, but it had little effect on modulation of mRNA expression of estrogen-responsive genes. However, blockade of Gper1 by its antagonist G-15 did not affect the inhibitory action of E2 on IGF-1-induced proliferation. Here, we demonstrate that E2 inhibition of lactotroph proliferation is due to nuclear ER-mediated genomic action. Our results suggest that activation of Gper1 mimics, but does not mediate, the anti-proliferative action of E2 on lactotrophs.
- Structural chromosome aberrations cause swelling of the nucleus. [Journal Article]
- GEGenes Environ 2016; 38:22
- CONCLUSIONS: These results strongly suggest that NS is mainly caused by structural aberrations in the nucleus during interphase of the cell cycle.
- A transgenic mouse model expressing an ERα folding biosensor reveals the effects of Bisphenol A on estrogen receptor signaling. [Journal Article]
- SRSci Rep 2016 Oct 10; 6:34788
- Estrogen receptor-α (ERα) plays an important role in normal and abnormal physiology of the human reproductive system by interacting with the endogenous ligand estradiol (E2). However, other ligands, ...
Estrogen receptor-α (ERα) plays an important role in normal and abnormal physiology of the human reproductive system by interacting with the endogenous ligand estradiol (E2). However, other ligands, either analogous or dissimilar to E2, also bind to ERα. This may create unintentional activation of ER signaling in reproductive tissues that can lead to cancer development. We developed a transgenic mouse model that constitutively expresses a firefly luciferase (FLuc) split reporter complementation biosensor (NFLuc-ER-LBDG521T-CFLuc) to simultaneously evaluate the dynamics and potency of ligands that bind to ERα. We first validated this model using various ER ligands, including Raloxifene, Diethylstilbestrol, E2, and 4-hydroxytamoxifen, by employing FLuc-based optical bioluminescence imaging of living mice. We then used the model to investigate the carcinogenic property of Bisphenol A (BPA), an environmental estrogen, by long-term exposure at full and half environmental doses. We showed significant carcinogenic effects on female animals while revealing activated downstream ER signaling as measured by bioluminescence imaging. BPA induced tumor-like outgrowths in female transgenic mice, histopathologically confirmed to be neoplastic and epithelial in origin. This transgenic mouse model expressing an ERα folding-biosensor is useful in evaluation of estrogenic ligands and their downstream effects, and in studying environmental estrogen induced carcinogenesis in vivo.
- Synthesis and basic evaluation of 7α-(3-[(18)F]fluoropropyl)-testosterone and 7α-(3-[(18)F]fluoropropyl)-dihydrotestosterone. [Journal Article]
- ANAnn Nucl Med 2016 Sep 28
- CONCLUSIONS: [(18)F]15 is better than [(18)F]7 in terms of radiochemical yield, in vitro binding affinity, prostate specific binding and stability against in vivo metabolic de-fluorination. However, the net uptake level of [(18)F]15 in prostate might be insufficient for in vivo visualization. Although [(18)F]7 and [(18)F]15 improved in vivo stability against de-fluorination, other basic characterization data in rodents were not superior to the current standard tracer 16β-[(18)F]fluoro-5α-dihydrotestosterone. It is also revealed that the shorter side chain length of 7α-[(18)F]fluoromethyl-dihydrotestosterone is superior to the longer three carbon chain in [(18)F]15, in terms of net prostate uptake and in vivo metabolic stability.
- Estrogenic compound profiles in an urbanized industry-impacted coastal bay and potential risk assessment by pollution indices and multivariative statistical methods. [Journal Article]
- MPMar Pollut Bull 2016 Sep 24
- The occurrence and distribution of target estrogenic compounds in a highly urbanized industry-impacted coastal bay were investigated, and contamination profiles were evaluated by estimating total est...
The occurrence and distribution of target estrogenic compounds in a highly urbanized industry-impacted coastal bay were investigated, and contamination profiles were evaluated by estimating total estradiol equivalents (∑EEQs) and risk quotients (RQs). Phenolic compounds were the most abundant xenoestrogens, but seldom showed contribution to the ∑EEQs. The diethylstilbestrol (DES) and 17α-ethinylestradiol (EE2) were the major contributors followed by 17β-estradiol (E2) in comparison with a slight contribution from estrone (E1) and estriol (E3). Both ∑EEQs and RQs indicated likely adverse effects posed on resident organisms. Further, multivariate statistical method comprehensively revealed pollution status by visualized factor scores and identified multiple "hotspots" of estrogenic sources, demonstrating the presence of complex pollution risk gradients inside and particularly outside of bay area. Overall, this study favors the integrative utilization of pollution indices and factor analysis as powerful tool to scientifically diagnose the pollution characterization of human-derived chemicals for better management decisions in aquatic environments.
- Using Fenton Oxidation to Simultaneously Remove Different Estrogens from Cow Manure. [Journal Article]
- IJInt J Environ Res Public Health 2016 Sep 15; 13(9)
- The presence of estrogens in livestock excrement has raised concerns about their potential negative influence on animals and the overall food cycle. This is the first investigation to simultaneously ...
The presence of estrogens in livestock excrement has raised concerns about their potential negative influence on animals and the overall food cycle. This is the first investigation to simultaneously remove estrogens, including estriol (E3), bisphenol A (BPA), diethylstilbestrol (DES), estradiol (E2), and ethinyl estradiol (EE2), from cow manure using a Fenton oxidation technique. Based on the residual concentrations and removal efficiency of estrogens, the Fenton oxidation reaction conditions were optimized as follows: a H₂O₂ dosage of 2.56 mmol/g, a Fe(II) to H₂O₂ molar ratio of 0.125 M/M, a solid to water mass ratio of 2 g/mL, an initial pH of 3, and a reaction time of 24 h. Under these conditions, the simultaneous removal efficiencies of E3, BPA, DES, E2, and EE2, with initial concentrations in cow manure of 97.40, 96.54, 100.22, 95.01, and 72.49 mg/kg, were 84.9%, 99.5%, 99.1%, 97.8%, and 84.5%, respectively. We clarified the possible Fenton oxidation reaction mechanisms that governed the degradation of estrogens. We concluded that Fenton oxidation technique could be effective for efficient removal of estrogens in livestock excrement. Results are of great importance for cow manure reuse in agricultural management, and can be used to reduce the threat of environmental estrogens to human health and ecological safety.
- Suppression of liver Apo E secretion leads to HDL/cholesterol immaturity in rats administered ethinylestradiol. [Journal Article]
- FOFEBS Open Bio 2016; 6(9):928-36
- Ethinylestradiol (EE), a main component of the combined oral contraceptive pill, is associated with an increased risk of arterial diseases. However, the toxicity mechanism of EE is poorly understood....
Ethinylestradiol (EE), a main component of the combined oral contraceptive pill, is associated with an increased risk of arterial diseases. However, the toxicity mechanism of EE is poorly understood. In this study, we found that the exposure to EE reduced the serum apolipoprotein E (Apo E) level and high-density lipoprotein (HDL)/cholesterol concentration in adult female rats. Diethylstilbestrol showed the same effects and both reductions were suppressed by coadministration of tamoxifen (TAM). Liver perfusion experiments revealed that the secretion rate of Apo E from the liver was significantly reduced. It is concluded that EE damages the maturation of HDL/cholesterol by delaying Apo E secretion from the liver, and this may lead to an increased risk of arterial diseases, such as atheromas.
- Uterine Clear Cell Carcinoma of Postmenopausal Woman: A Case Report. [Journal Article]
- JMJ Menopausal Med 2016; 22(2):122-5
- Endometrial cancer is the most common gynecologic malignancy in developed countries. Clear cell carcinoma typically occurs in the ovaries, and very rarely occurs in the endometrium; it accounts for l...
Endometrial cancer is the most common gynecologic malignancy in developed countries. Clear cell carcinoma typically occurs in the ovaries, and very rarely occurs in the endometrium; it accounts for less than 3% of all endometrial cancers. It is presumed that clear cell carcinomas are of Müllerian duct origin, and an association with exposure to diethylstilbestrol (DES) or other nonsteroidal follicle stimulating hormones has been described. We report a case of a postmenopausal woman who presented with vaginal bleeding without a specific medical history. Under the impression of an endometrial mass, we performed a laparoscopic operation. Pathologic results showed clear cell carcinoma of the endometrium. Depth of invasion was 0.2 cm out of a 0.5 cm total thickness, and the rectal shelf mass was clear cell carcinoma. We report the case with a brief review of the relevant literature.
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- Mammary Gland Evaluation in Juvenile Toxicity Studies: Temporal Developmental Patterns in the Male and Female Harlan Sprague-Dawley Rat. [Journal Article]
- TPToxicol Pathol 2016; 44(7):1034-58
- There are currently no reports describing mammary gland development in the Harlan Sprague-Dawley (HSD) rat, the current strain of choice for National Toxicology Program (NTP) testing. Our goals were ...
There are currently no reports describing mammary gland development in the Harlan Sprague-Dawley (HSD) rat, the current strain of choice for National Toxicology Program (NTP) testing. Our goals were to empower the NTP, contract labs, and other researchers in understanding and interpreting chemical effects in this rat strain. To delineate similarities/differences between the female and male mammary gland, data were compiled starting on embryonic day 15.5 through postnatal day 70. Mammary gland whole mounts, histology sections, and immunohistochemically stained tissues for estrogen, progesterone, and androgen receptors were evaluated in both sexes; qualitative and quantitative differences are highlighted using a comprehensive visual timeline. Research on endocrine disrupting chemicals in animal models has highlighted chemically induced mammary gland anomalies that may potentially impact human health. In order to investigate these effects within the HSD strain, 2,3,7,8-tetrachlorodibenzo-p-dioxin, diethylstilbestrol, or vehicle control was gavage dosed on gestation day 15 and 18 to demonstrate delayed, accelerated, and control mammary gland growth in offspring, respectively. We provide illustrations of normal and chemically altered mammary gland development in HSD male and female rats to help inform researchers unfamiliar with the tissue and may facilitate enhanced evaluation of both male and female mammary glands in juvenile toxicity studies.