• Korean Journal of Microbiology
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• v.44 no.1
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• pp.37-42
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• 2008

Optimal conditions for the biodegradation of endocrine-disrupting bisphenol A (BPA) were examined for the white rot fungus Trametes versicolor isolated in Korea. T. versicolor degraded 100% of 50 mg/L bisphenol A during 12 hr in yeast extract-malt extract-glucose (YMG) medium. When BPA was added to the 5-day preincubated fungal culture in YMG medium, all BPA was removed in 2 hr. T. versicolor could efficiently degrade BPA at $35^{\circ}C$, pH 6 in YMG medium. T. versicolor could more easily remove BPA of $1{\sim}25\;mg/L$ than that of higher concentrations ($50{\sim}100\;mg/L$) in YMG medium. T. versicolor degraded 100% of 50 mg/L BPA for 36 h in a minimal medium, which is lower degradation rate than that in YMG medium. Optimal conditions for BPA biodegradation in the minimal medium were similar to those in YMG medium. When BPA (50 mg/L) was added into domestic wastewater, it could be completely removed by T. versicolor. During the biodegradation of BPA by T. versicolor in YMG medium, its estrogenic activity decreased.

• Journal of Microbiology and Biotechnology
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• v.30 no.2
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• pp.178-186
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• 2020

Licorice (Glycyrrhiza uralensis) contains several compounds that have been reported to alleviate menopausal symptoms via interacting with estrogen receptors (ERs). The compounds exist mainly in the form of glycosides, which exhibit low bioavailability and function. To bioconvert liquiritin and isoliquiritin, the major estrogenic compounds, to the corresponding deglycosylated liquiritigenin and isoliquiritigenin, respectively, licorice was fermented with Monascus, which has been demonstrated to deglycosylate other substances. The contents of liquiritigenin and isoliquiritigenin in Monascus-fermented licorice increased by 10.46-fold (from 38.03 μM to 379.75 μM) and 12.50-fold (from 5.53 μM to 69.14 μM), respectively, compared with their contents in non-fermented licorice. Monascus-fermented licorice exhibited 82.5% of the ERβ binding activity of that observed in the positive control (17 β-estradiol), whereas the non-fermented licorice exhibited 54.1% of the binding activity in an in vivo ER binding assay. The increase in the ERβ binding activity was associated with increases in liquiritigenin and isoliquiritigenin contents. Liquiritigenin acts as a selective ligand for ERβ, which alleviates menopausal symptoms with fewer side effects, such as heart disease and hypertension, compared with a ligand for ERα. In addition, Monascus-fermented licorice contained 731 mg/kg of monacolin K, one of the metabolites produced by Monascus that reduces serum cholesterol. Therefore, Monascus-fermented licorice is a promising material for the prevention and treatment of menopausal syndrome with fewer side effects.

• Toxicological Research
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• v.20 no.3
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• pp.205-211
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• 2004

Concern that some chemicals in our environment may affect human health by disrupt-ing normal endocrine function has prompted a research on interactions of environmental contaminants with steroid hormone receptor. Toxaphene and chlordane are among the 12 persistent organic pollutants identified by the United Nations Environment Programme as requiring urgent attention. We compared the estrogenic activity of two organochlorine pesticides, toxaphene and chlordane, at estrogen receptor a (ER$\alpha$) and estrogen receptor $\beta$ (ER$\beta$). Human hepatoma cells (HepG2) were transiently transfected with rat ER$\alpha$ or ER$\beta$ plus an estrogen-responsive complement C3-luciferase (C3-Luc) reporter gene. After transfection, cells were treated with various concentrations of toxaphene and chlordane to investigate agonism or antagonism of these chemicals. Both toxaphene and chlordane were potent agonists in HepG2 cells for ER$\alpha$. In contrast, these chemicals had a minimal agonist activity with ER$\beta$ and almost abolished 17$\beta$-estradiol-induced ER$\beta$-mediated activity. Therefore, toxaphene and chlordane behaved as an ER$\alpha$ agonist and an ER$\beta$ antagonist with estrogen-responsive reporter plasmid C3-Luc, and exposure to these organochlorine pesticides could have a crictical effect on normal endocrine function.

• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 2002.10a
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• pp.170-170
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• 2002

College of Pharmacy, Ewha womans University, Seoul, 120-750, Korea 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is the most potent halogenated aromatic hydrocarbon congener that induces expression of several genes including CYP1A1. Exposure to TCDD results in many toxic actions such as carcinogenesis, hepatotoxicity, immune suppression, and reproductive and developmental toxicity. Dramatic differences in dioxin toxicity have been observed between the sexes of some animal species, suggesting hormonal modulation of dioxin action. Many studies have been reported and propose several mechanisms of anti-estrogenic effects of TCDD. In contrast, the effect of estrogen on the regulation of CYP1A1 are not clear at present. There are several reports showing conflicting results. It seems that induction/inhibition of CYP1A1 may be dependent on cell-type and concentration. The purpose of this study was to investigate the regulation of TCDD-induced CYP1A1 gene expression by estradiol and its metabolites. We examined whether estradiol and its metabolites altered TCDD-mediated induction of CYP1A1 enzyme activity. 17 ${\beta}$ estradiol and 16 ${\alpha}$ estriol at non cytotoxic concentrations caused a significant concentration dependent decline of TCDD-induced EROD activity To determine whether reduced EROD activity reflected altered CYP1A1 mRNA expression, we measured CYP1A1 mRNA level by RT-PCR. And to examine whether estradiol and its metabolites have effects on TCDD-induced CYP1A1 gene expression at the transcription level, we also peformed transient transfection with an AhR responsive reporter plasmid containing the 5' flanking region of the human CYP1A1 gene to examine whether estradiol and its metabolites have effects on TCDD-induced CYP1A1 gene expression at the transcription level.

• Development and Reproduction
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• v.23 no.4
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• pp.333-344
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• 2019

In vertebrate reproductive system, estrogen receptor (ER) plays a pivotal role in mediation of estrogenic signaling pathways. In the present study, we report the cDNA cloning, expression analysis, and transcriptional activity of ERβ1 subtype from medaka Oryzias dancena. The deduced O. dancena ERβ1 (odERβ1; 519 amino acids) contained six characteristic A/B to E/F domains with very short activation function 2 region (called AF2). A phylogenetic analysis indicated that odERβ1 was highly conserved among teleost ERβ1 subgroup. A conventional RT-PCR revealed that the odERβ1 transcripts were widely distributed in the multiple tissues, the ovary, brain, gill, intestine, kidney, and muscle. Further, the relatively higher odERβ1 expressions in the ovary and brain were clearly reproduced in RT-qPCR assay. When HA-fused odERβ1 expression vector was transfected into HEK293 cells, an immunoreactivity for odERβ1 was mainly detected in the nucleus part. Finally, an estrogen responsive element driven luciferase reporter assays demonstrated that the transcriptional activity of odERβ1 significantly increased by estradiol-17β (E2) in a dose dependent manner (p<0.05). However, fold-activation of odERβ1 in the presence of E2 was markedly weak, when it compared with those of O. latipes ERβ1. Taken together, these data suggest that odERβ1 represents a functional variant of teleost ERβ subtype and provides a basic tool allowing future studies examining the function of F domain of ERβ1 subtype and expanding our knowledge of ERβ evolution.

• Biomolecules & Therapeutics
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• v.17 no.2
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• pp.188-198
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• 2009

This work was conducted to investigate the effect of bisphenol A (BPA) on estradiol (E2) 2-and 4-hydroxylase activities in the liver, kidney and lung tissues of male and female rats. After intraperitoneal administration of BPA to male and female rats for 4 days at 0, 10, and 50 mg/kg, the conversion of the substrate for hepatic and extra-hepatic enzyme activities was measured by GC/MSD. The result showed decreases of body and organ weights at 50 mg/kg BPA of male and female rats. Male hepatic E2 2-hydroxylase activity was inhibited by 68% at 10 mg/kg and by 82% at 50 mg/kg BPA. Female hepatic E2 2-hydroxylase activity was decreased by 46% at 10 mg/kg and by 56% at 50 mg/kg to the control. E2 4-hydroxylase was inhibited by 57 and 57% at 10 mg/kg and 54 and 78% at 50 mg/kg in liver of female and male, respectively. The urinary excretion rate of 2-hydroxyestradiol (2-OHE), androsterone and testosterone in urine of female rats with 50 mg/kg BPA were decreased significantly. The results showed that 50 mg/kg BPA was decreased E2 2-and 4-hydroxylase activities in liver, but not in other tissues. The urinary excretion rates of 2-OHE, androsterone and testosterone were also decreased. In liver, estrogenic enzyme activity were higher in male than female. These results suggest that BPA can disrupt estrogen metabolism by suppressing E2 2-and 4-hydroxylase activities in the liver of male and female rats.

• The Korean Journal of Pharmacology
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• v.26 no.2
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• pp.167-176
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• 1990

In the present study, we examined the effects of tamoxifen and LY117018 on various parameters for the estrogenic actions in order to understand the mechanism by which tamoxifen and LY117018 act on the uterine cells in 21-23 day old immature rats. Tamoxifen and LY117018 stimulated uterine weight and uterine contents of DNA, protein, and peroxidase activity in the absence of estradiol while inhibited above parameters in the presence of estradiol. Both cytosolic and nuclear progesterone receptors were increased by the treatment of tamoxifen and LY117018 as well as estradiol, but estradiol-induced increase in the progesterone receptors were reduced by the treatment of antiestrogens. These effects were enhanced by the multiple injections of antiestrogens. It seemed that tamoxifen was more agonistic than LY117018 but less antagonistic than LY117018, judged by their effects on various parameters for the estrogenic action. The affinities of estradiol, tamoxifen, and LY117018 for the estrogen receptor were $0.17{\pm}0.01nM(100%)$, $1.10{\pm}0.01nM(6.3%)$, and $0.23{\pm}0.01nM(77%)$, respectively. Furthermore, LY117018 was the competitive ligand for the estrogen receptor in dose-related manner but tamoxifen was not. Following estradiol treatment, nuclear estrogen receptor was sharply increased by 1 h, reaching the maximum by 16 h, while tamoxifen and LY117018 slightly increased nuclear estrogen receptor by 1 h and then decreased thereafter. It is therefore concluded that LY117018 is a competitive antagonist for the estrogen receptor with less estrogenic activity, compared to tamoxifen with low affinity to the estrogen receptor, and tamoxifen may act through other binding site than the estrogen receptor.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.3
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• pp.326-332
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• 2010

Daidzein, a natural isoflavonoid phytoestrogen, structurally resembles estradiol (E2) and possesses estrogenic activity. This study was designed to test the hypothesis that daidzein may mimic the effects of E2 on ovine follicle development by regulation of the mRNA expression of bone morphogenetic protein receptor genes and thereby influence the reproductive system. Granulosa cells were cultured in serum-free McCoy's 5A medium with and without supplementation of daidzein. Results showed that daidzein (10-100 ng/ml) significantly increased the proliferation of ovine granulosa cells (p<0.05), but inhibited the growth of granulosa cells at a dose of 1,000 ng/ml (p<0.01). Daidzein inhibited progesterone production in a dose dependent manner; however, it did not affect estradiol production by granulosa cells. We also investigated the effects of daidzein on BMPRII, BMPRIB and ALK-5 mRNA expression in ovine granulosa cells by quantitative real-time PCR. Treatment of granulosa cells with daidzein increased significantly expression of these genes at 10-100 ng/ml. Thus, these data suggested that a low concentration of daidzein (10-100 ng/ml) had a direct stimulatory effect on ovine granulosa cells while a high concentration was toxic.

• Proceedings of the Korea Environmental Mutagen Society Conference
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• 2002.11a
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• pp.166-166
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• 2002

• Journal of Applied Biological Chemistry
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• v.48 no.2
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• pp.49-57
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• 2005

Soy is an important food in Asia and many studies have suggested that the low incidences of chronic diseases in Asian countries are associated with diets that are rich in soy. Soy contains many kinds of phytochemicals, and soy isoflavones and soyasaponins have received considerable attention. Twelve isoflavone components have been isolated from soy: three aglycones (daidzein, genistein, and glycitein), and their respective nine glucosidic conjugates. Soy isoflavones are similar in structure to estrogen and exhibit both estrogenic and antiestrogenic activities. Soy isoflavones exhibit anticancer activity, can reduce the risk of cardiovascular disease, and are beneficial to brain and bone health. Soyasaponins are divided into three groups (A, B, and E saponins), and they exhibit hypocholesterolemic, anticancer, hepatoprotective, antioxidative, and anti-human-immunodeficiency-virus effects. Despite the abundant literature suggesting that soy isoflavones and soyasaponins have potential applications in preventive medicine, further research is needed to standardize dosages and ensure their efficacy.