• Molecular & Cellular Toxicology
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• v.1 no.3
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• pp.149-156
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• 2005

Di (n-ethylhexyl) phthalate (DEHP) is thought to mimic estrogens in their action, and are called endocrine disrupting chemicals. DEHP is used in numerous consumer products, especially those made of flexible polyvinyl chloride and have been reported to be weakly estrogenic. In this study, DEHP were tested for estrogenic properties in vitro models and with microarray analysis. First, the E-screen assay was used to measure the proliferation of DEHP in MCF-7 cells, a human breast cancer cell line. DEHP induced an increase in MCF-7 cell proliferation at concentration of $10^{-4}M$. Second, we carried out a microarray analysis of MCF-7 cells treated with DEHP using human c-DNA microarray including 401 endocrine system related genes. Of the genes analyzed, 60 genes were identified showing significant changes in gene expression resulting from DEHP. Especially, 4 genes were repressed and 4 genes were induced by DEHP compared to $17{\beta}-estradiol$. Among these genes, trefoil factor 3 (intestinal), breast cancer 1, early onset and CYP1B1 are involved in estrogen metabolism and regulation. Therefore it suggests that these genes may be associated with estrogenic effect of the DEHP on transcriptional level. The rationale is that, as gene expression is a sensitive endpoint, alterations of these genes may act as useful biomarkers to define more precisely the nature and level of exposure to kinds of phthalates.

• Journal of Food Hygiene and Safety
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• v.14 no.4
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• pp.408-414
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• 1999

A number of chemical released into the environment eliciting their effects by disrupting normal hormonal pathways. Endocrine disrupting compounds are present in the aquatic environment and pose potential health consequences to wildlife and humans. This review are designing fur xenobiotic estrogens based on induction of the egg-yolk precursor protein vitelloge-nin. In fish of aquatic environment, it may result in decrease fertility and egg production in females or lead to reduced gonad size or feminization of genetic male fish. It has been known that male fish exposed to estrogenic compounds show induced production of vitellogenin. Vitello-genin production is normally restricted to adult females, which have elevated estrogen levels during egg production. However, vitellogenin can be induced in males by Pollution of environmental endocrine disruptors. Consequently, the presence of vitellogenin in male fish can serve as an indicator of exposure of environmental endocrine disrupting compounds. In immature fish pol-luted at low levels of environmental endocrine disrupter, vitellogenin can serve as a reliable biomarker for exposure to endocrine disrupter. This review demonstrates the utility of vitellogenin as a biomarker fur exposure to estrogenin agents in auqatic environment.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.48 no.4
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• pp.483-488
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• 2015

We studied oocyte steroidogenesis in the blackfin flounder Glyptocephalus stelleri as a region-specific species, in the East Sea of Korea during the spawning season. Maturing oocytes (0.76, 0.82, 0.88, and 0.91 mm in oocyte diameter) were incubated in vitro in the presence of [$^3H$] $17{\alpha}$-hydroxyprogesterone ($[^3H]17{\alpha}$-OHP) as a precursor. Steroid metabolites were extracted from the incubated medium and oocytes, and the extracts were separated and identified by thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC) and gas chromatographymass spectrometry (GC/MS). The major metabolites produced from $[^3H]17{\alpha}$-OHP were androgens [androstenedione (A4) and testosterone (T)] and estrogens [$17{\beta}$-estradiol (E2) and estrone (E1)] and progestins [$17{\alpha},20{\alpha}$-dihydroxy-4-pregen-3-one ($17{\alpha}20{\alpha}P$) and $17{\alpha}20{\beta}$-dihydroxy-4-pregnen-3-one ($17{\alpha}20{\beta}P$)] in maturing oocytes. The metabolic rate of $17{\alpha}20{\beta}$ was elevated (29.04%) in oocytes measuring 0.88 mm (nucleus migration stage following the induction of germinal vesicle breakdown), but was very low in oocytes measuring 0.76, 0.82, and 0.91 mm (0.42, 0.67, and 2.62%, respectively). From these results, we suggest that $17{\alpha}20{\beta}P$ acts as a maturation-inducing steroid in the blackfin flounder.

• Clinical and Experimental Pediatrics
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• v.45 no.2
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• pp.278-283
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• 2002

Imperforated hymen, vaginal atresia or high transverse vaginal septum are caused by incomplete vaginal canalization. The infant may be present with distention of the vagina and the uterus with glandular secretions stimulated by maternal estrogens, known as hydrometrocolpos. We report two cases of hydrometrocolpos. In the first case, distal vaginal atresia with cystovaginal fistula was revealed by a contrast fluoroscope through the percutaneous catheterization. In the second case, urogenital sinus was detected by a fistulogram through a single orifice in the genital area. We decompressed the cystic mass by ultrasonogram guided aspiration, promptly at birth, then achieved the transient drainage of cystic fluids by percutaneous catheterization.

• Environmental Engineering Research
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• v.21 no.2
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• pp.188-195
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• 2016

$17{\alpha}$-Ethynylestradiol (EE2) has gotten growing concerns due to its widely detected in the environment and high estrogenic potency. However, the knowledge on the photochemical behaviors of EE2 in natural waters is still limited. Herein, the photodegradation and estrogenic potency variation of EE2 induced by nitrate were studied using a sunlight simulator consisted by a 300 W medium pressure mercury lamp and 290 nm cut-off filters. It was found that EE2 could be photodegraded at a rate of $0.0193h^{-1}$ in pure aqueous solutions, and the photodegradation of EE2 could be significantly promoted by nitrate. The photodegradation removal rate of EE2 was increased from 9% in Milli-Q water to 85% in 2.0 mM nitrate solutions. Reactive species scavenging experiments demonstrated that the photogenerated $HO{\bullet}$ contributed about 55% to EE2 degradation. Fe(III), Cl- and dissolved humic acid (DHA) could inhibit the photodegradation of EE2 by competing the incident light and photogenerated $HO{\bullet}$, while $HCO_3{^-}$ had no influence on EE2 photodegradation. EE2 was determined to be phototransformed into organic chemicals without estrogenic potency by GC-MS and MCF-7 cell proliferation toxicity tests. These findings could extend our knowledge on the photochemical behaviors of steroid estrogens and provide information for ecological risk assessment.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.40 no.3
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• pp.153-159
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• 2007

We studied oocyte steroidogenesis in relation to oocyte development in the greenling, Hexagrammos otakii, a marine multiple spawner. Vitellogenic and mature oocytes were incubated in vitro in the presence or absence of $[^3H]-17\;{\alpha}-hydroxyprogesterone$ as a precursor. The major metabolites were androgens [androstenedione $(A)_4)$ and testosterone (T)] and estrogens [$17\;{\beta}-estradiol\;(E_2)$ and estrone ($E_1$)] in vitellogenic oocytes. The metabolic rate of T was lower in 1.08 to 12-mm oocytes, while that of $E_2$ increased with oocyte size. The endogenous productions of T, $E_2$ and 17 ${\alpha}-hydroxy$, 20 ${\beta}-dihydroprogesterone\;(17{\alpha}20{\beta}OHP)$ were quantified using a radioimmunoassay in the non-precursor group. The endogenous levels of T and $E_2$ were highest in 1.08 to 12-mm oocytes and $17{\alpha}20{\beta}OHP$ was produced only in 1.90 to 95-mm oocytes. The relationship between oocyte size and steroidogenesis showed that 1.08 to 12-mm oocytes are full vitellogenic following induction of the maturation process. Moreover, $17{\alpha}20{\beta}OHP$ acts as a maturation inducing hormone in H. otakii.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.112-112
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• 2001

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental toxin that activates the aryl hydrocarbon receptor (AhR) and disrupts multiple endocrine signaling pathways by enhancing ligand metabolism, altering hormone synthesis, down regulating receptor levels, and interfering with gene transcription. And TCDD-mediated gene transactivation via the AhR has been shown to be dependent upon estrogen receptor (ER) expression in human breast cancer cells. In the present study, we have examined the effect of natural estrogen, phytoestrognes and environmental estrogens on the regulation of CYP1A1 gene expression in MCF-7 human breast cancer cell line. that ER and AhR are co-expressed. pCYP1A1 -luc reporter gene was transiently transfected into MCF-7 cells. These cells were treated with various chemicals and then luciferase assay was carried out. 17be1a-estradiol significantly inhibited TCDD stimulated luciferase activity dose dependently and this inhibition was partially recovered by concomitant treatment of tamoxifen. 17beta-estradiol metabolites, 2-hydroxyestradiol and 16alpha-estriol resulted in less potent inhibitory effect than estradiol and synthetic estrogen, diethylstilbestrol (DES) showed no effect on CYP1A1 gene expression. This study demonstrated that estrogen down-regulated TCDD stimulated CYP1A1 expression via ER mediation. And we have found out that several flavonoids such as genistein, kaempferol, daidzein, naringenin, and alkylphenols such as nonylphenol, 4-octylphenol and resveratrol also inhibited TCDD induced CYP1A1 expression like estrogen.

• Mass Spectrometry Letters
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• v.4 no.4
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• pp.59-66
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• 2013

A metabolomics study was conducted to identify urinary biomarkers for breast cancer, using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-mass spectrometry (LC-MS), analyzed by principal components analysis (PCA) as well as a partial least squares-discriminant analysis (PLS-DA) for a metabolic pattern analysis. To find potential biomarkers, urine samples were collected from before- and after-mastectomy of breast cancer patients and healthy controls. Androgens, corticoids, estrogens, nucleosides, and polyols were quantitatively measured and urinary metabolic profiles were constructed through PCA and PLS-DA. The possible biomarkers were discriminated from quantified targeted metabolites with a metabolic pattern analysis and subsequent screening. We identified two biomarkers for breast cancer in urine, ${\beta}$-cortol and 5-methyl-2-deoxycytidine, which were categorized at significant levels in a student t-test (p-value < 0.05). The concentrations of these metabolites in breast cancer patients significantly increased relative to those of controls and patients after mastectomy. Biomarkers identified in this study were highly related to metabolites causing oxidative DNA damage in the endogenous metabolism. These biomarkers are not only useful for diagnostics and patient stratification but can be mapped on a biochemical chart to identify the corresponding enzyme for target identification via metabolomics.

• Journal of Periodontal and Implant Science
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• v.48 no.5
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• pp.284-294
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• 2018

Purpose: Epithelial barrier dysfunction is involved in the pathophysiology of periodontitis and oral lichen planus. Estrogens have been shown to enhance the physical barrier function of intestinal and esophageal epithelia, and we aimed to investigate the effect of estradiol (E2) on the regulation of physical barrier and tight junction (TJ) proteins in human oral epithelial cell monolayers. Methods: HOK-16B cell monolayers cultured on transwells were treated with E2, an estrogen receptor (ER) antagonist (ICI 182,780), tumor necrosis factor alpha ($TNF{\alpha}$), or dexamethasone (Dexa), and the transepithelial electrical resistance (TER) was then measured. Cell proliferation was measured by the cell counting kit (CCK)-8 assay. The levels of TJ proteins and nuclear translocation of nuclear factor $(NF)-{\kappa}B$ were examined by confocal microscopy. Results: E2 treatment increased the TER and the levels of junctional adhesion molecule (JAM)-A and zonula occludens (ZO)-1 in a dose-dependent manner, without affecting cell proliferation during barrier formation. Treatment of the tight-junctioned cell monolayers with $TNF{\alpha}$ induced decreases in the TER and the levels of ZO-1 and nuclear translocation of $NF-{\kappa}B$. These $TNF{\alpha}-induced$ changes were inhibited by E2, and this effect was completely reversed by co-treatment with ICI 182,780. Furthermore, E2 and Dexa presented an additive effect on the epithelial barrier function. Conclusions: E2 reinforces the physical barrier of oral epithelial cells through the nuclear ER-dependent upregulation of TJ proteins. The protective effect of E2 on the $TNF{\alpha}-induced$ impairment of the epithelial barrier and its additive effect with Dexa suggest its potential use to treat oral inflammatory diseases involving epithelial barrier dysfunction.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.387-393
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• 2016

Background: CYP1A1 is a candidate gene for low-penetrance breast cancer susceptibility, as it plays an important role in the metabolism of carcinogens and estrogens. Purpose: The objective of this study was to assess the association between M2 (A2455G, Ile462Val) and M4 (C2453A, Thr461Asn) polymorphisms in CYP1A1 and breast cancer risk among Jordanian women and in subgroups stratified by menopausal status and smoking history. Materials and Methods: Blood samples were collected from 112 breast cancer female patients and 115 age-matched controls who underwent breast cancer screening with imaging and showed negative results (BI-RADS I or BI-RADS II). Genotyping was performed using the PCR-RFLP technique. Results: No statistically significant overall association was found between breast cancer risk and CYP1A1 M2 genotypes (p= 0.55; OR = 0.77; 95% CI= 0.32 - 1.83) nor with the M4 polymorphism (p= 0.95; OR= 0.95; 95% CI= 0.51 - 1.88). Analysis of subgroups defined by menopausal status or smoking history also revealed no association with these polymorphisms. Furthermore, the four identified haplotypes (AC; AA; GC and GA) were equally distributed among cases and controls, and haplotype analysis showed a strong linkage disequilibrium of both studied loci in either cases or controls (D'=1). Conclusions: Based on the study results, CYP1A1 M2 and M4 polymorphisms do not seem to play a major role in breast cancer risk among Jordanian females.