• 한국환경성돌연변이발암원학회지
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• 제22권4호
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• pp.274-278
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• 2002

Phthalates, suspected endocrine disruptor, are plasticizer and solvent used in industry, and some phthalates are known as potential carcinogen. Most common human exposure to this compounds may occur with contaminated food. It may migrate into food from plastic wrap or may enter food from general environmental contamination, and it has become widespread environmental pollutants, thus leading to a variety of phthalates that possibly threaten the public health. Dibutyl phthalate (DBP) may playa part of cell proliferator, which mediates changes in gene expression and the metabolism of xenobiotics. An understanding of the role of DBP in modulating gene regulation should provide insight regarding mechanisms of DBP induced xenoestrogenic impact. To elucidate the type of genes that are associated with estrogenic activity induced by DBP at the dose (10$^{-8}$ M) appeared proliferating effects, the pattern of gene expression in MCF7 cells was compared between 17$\beta$-estradiol and DBP exposure in the cDNA microarray. From the results, it showed some differences of gene expression patterns between MCF7 cells treated with 17$\beta$-estradiol and DBP, and also DBP shows estrogenic potential with changes in estrogen-related gene expression levels.

• 농약과학회지
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• 제8권2호
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• pp.95-102
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• 2004

현재 국내 사용중이며 내분비계 장애추정농약으로 분류된 benomyl, carbaryl, endosulfan등 17종 농약에 대한 estrogen성 영향을 검색하기 위하여 인체난소암세포(BG1Luc4E2)를 이용한 luciferase assay를 수행하였으며, luciferase assay에서 Eeq를 산출한 후 내분비계 장애추정 농약의 에스트로겐성 영향에 대한 식이섭취 위험도 평가를 실시하였다. Estrogen 수용체 결합시험에서 cypermethrin, dicofol, endosulfan, esfenvalerate 및 fenvalerate가 $10^{-5}$ M에서 최고 영향이 관찰되었고, mancozeb 등 8종 농약은 약한 영향이 관찰되었으며, benomyl 등 나머지 4종 농약은 영향이 없었다. 이들 중 활성이 비교적 강한 dicofol 및 endoeulfan의 1 nmol 17 $\beta$-estradiol에 대한 RLP 와 RLU는 dicofol의 경우 $10^{-5}$ 및 56%이었구, endosulfan은 $10^{-5}$ 및 72%이었다. MRL을 이용한 식이섭취 위험도 평가 결과 농약들의 추청 1일 최대농약섭취량은 cypermethrin 0.667, dicofol 0.1462, endosulfan 0.2066 및 lenvalerate/esfenvalerate 0.2098 mg/person으로 총 추정 1일 최대 농약섭취량이 1.2298 mg/person이었고, 남성 혈중 에스트로겐 증가 농도는 3.075 ng/L로 정상농도에 비해 15%정도 증가하였으나, 국내 모니터링 성적을 기준으로 평가한 결과 남성혈중 에스트로겐 증가 농도는 0.01938 ng/L로 정상농도에 비해 0.09693%정도 증가하였다.

• 한국식품과학회지
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• 제47권5호
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• pp.667-672
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• 2015

저성장 어린이들을 대상으로 하는 성장호르몬 치료는 다양한 부작용과 투여과정의 스트레스로 인한 환자 순응도 감소, 고가의 치료 비용 등의 단점을 가지고 있다. 이러한 이유로 부작용 발생의 위험성이 작고 낮은 비용으로 어린이의 성장에 도움을 줄 수 있는 천연물 유래 기능성 소재 개발에 대한 관심이 증가하고 있다. 그러나 성적으로 미성숙 상태인 어린이를 대상으로 한다는 점, 에스트로겐에 의한 뼈 성장과 성조숙증 발병기전 연관성, 천연물에 존재하는 다양한 식물성 에스트로겐의 영향으로 안전성에 대한 우려가 존재하는 것이 사실이다. 따라서 본 연구에서는 앞선 연구를 통하여 뼈 성장 촉진 효과가 확인된 시험물질의 안전성을 확인하기 위하여 난소를 절제한 실험동물에 시험물질을 4주간 투여한 후 시험물질이 식물성 에스트로겐으로 작용하여 성조숙증과 성장호르몬 이상을 일으킬 가능성을 확인하고자 하였다. 실험 결과 난소 절제로 인한 체중증가, 혈중 지질 농도의 증가, 자궁 벽 두께의 감소 등이 나타남을 확인하였으며 시험물질의 4주 투여가 이러한 변화에 영향을 끼치지 않음을 확인할 수 있었다. 또한 혈중 에스트로겐 농도, 혈중 성장호르몬 농도를 분석한 결과 시험물질 투여가 아무런 영향을 주지 않음을 확인하였다. 이러한 결과는 백수오와 한속단 동량 혼합물이 생체 내에서 식물성 에스트로겐으로 작용하지 않는다는 것을 의미하며 반복투여에 의한 성장호르몬 이상을 일으키지 않는 것으로 판단된다.

• Journal of Ginseng Research
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• 제43권4호
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• pp.527-538
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• 2019

Background: Ginsenoside Rg1 was shown to exert ligand-independent activation of estrogen receptor (ER) via mitogen-activated protein kinase-mediated pathway. Our study aimed to delineate the mechanisms by which Rg1 activates the rapid ER signaling pathways. Methods: ER-positive human breast cancer MCF-7 cells and ER-negative human embryonic kidney HEK293 cells were treated with Rg1 ($10^{-12}M$, $10^{-8}M$), $17{\beta}$-estradiol ($10^{-8}M$), or vehicle. Immunoprecipitation was conducted to investigate the interactions between signaling protein and ER in MCF-7 cells. To determine the roles of these signaling proteins in the actions of Rg1, small interfering RNA or their inhibitors were applied. Results: Rg1 rapidly induced $ER{\alpha}$ translocation to plasma membrane via caveolin-1 and the formation of signaling complex involving linker protein (Shc), insulin-like growth factor-I receptor, modulator of nongenomic activity of ER (MNAR), $ER{\alpha}$, and cellular nonreceptor tyrosine kinase (c-Src) in MCF-7 cells. The induction of extracellular signal-regulated protein kinase and mitogen-activated protein kinase kinase (MEK) phosphorylation in MCF-7 cells by Rg1 was suppressed by cotreatment with small interfering RNA against these signaling proteins. The stimulatory effects of Rg1 on MEK phosphorylation in these cells were suppressed by both PP2 (Src kinase inhibitor) and AG1478 [epidermal growth factor receptor (EGFR) inhibitor]. In addition, Rg1-induced estrogenic activities, EGFR and MEK phosphorylation in MCF-7 cells were abolished by cotreatment with G15 (G protein-coupled estrogen receptor-1 antagonist). The increase in intracellular cyclic AMP accumulation, but not Ca mobilization, in MCF-7 cells by Rg1 could be abolished by G15. Conclusion: Ginsenoside Rg1 exerted estrogenic actions by rapidly inducing the formation of ER containing signalosome in MCF-7 cells. Additionally, Rg1 could activate EGFR and c-Src ER-independently and exert estrogenic effects via rapid activation of membrane-associated ER and G protein-coupled estrogen receptor.

• Journal of Microbiology and Biotechnology
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• 제18권4호
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• pp.767-772
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• 2008

Biodegradation of endocrine-disrupting phthalates [diethyl phthalate (DEP), dimethyl phthalate (DMP), butylbenzyl phthalate (BBP)] was investigated with 10 white rot fungi isolated in Korea. When the fungal mycelia were added together with 100 mg/l of phthalate into yeast extract-malt extract-glucose (YMG) medium, Pleurotus ostreatus, Irpex lacteus, Polyporus brumalis, Merulius tremellosus, Trametes versicolor, and T. versicolor MrP1 and MrP13 (transformant of the Mn-repressed peroxidase gene of T. versicolor) could remove almost all of the 3 kinds of phthalates within 12 days of incubation. When the phthalates were added to 5-day pregrown fungal cultures, most fungi except I. lacteus showed the increased removal of the phthalates compared with those of the non-pregrown cultures. In both culture conditions, p. ostreatus showed the highest degradation rates for the 3 phthalates tested. BBP was degraded with the highest rates among the 3 phthalates by all fungal strains. Only 14.9% of 100 mg/I BBP was degraded by the supernatant of P. ostreatus culture in YMG medium in 4 days of incubation, but the washed or homogenized mycelium of P. ostreatus could remove 100% of BBP within 2 days even in distilled water, indicating that the initial BBP biodegradation by P. ostreatus may be attributed to mycelium-associated enzymes rather than extracellular enzymes. The biodegradation rate of BBP by the immobilized cells of P. ostreatus was almost same as that in the suspended culture. The estrogenic activity of 100 mg/I DMP decreased during biodegradation by P. ostreatus.

• 한국환경성돌연변이발암원학회지
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• 제22권3호
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• pp.175-182
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• 2002

Endocrine disruptors (EDs) are the chemicals that affect endocrine systems through activation or inhibition of steroid hormone response. It is necessary to have a good system to evaluate rapidly and accurately endocrine-disrupting activities of suspected chemicals and their degradation products. The key targets of EDs are nuclear hormone receptors, which bind to steroid hormones and regulate their gene transcription. We constructed a co-expression system of Gal4p DNA binding domain (DBD)- ligand binding domain of human estrogen receptor $\alpha$ or $\beta$, and Gal4p transactivation domain (TAD)-co-activator AIB-1, SRC-1 or TIF-2 in Saccharomyces cerevisiae with a chromosome-integrated lacZ reporter gene under the control of CYC1 promoter and Gal4p binding site (GAL4 upstream activating sequence, GAL4$_{UAS}$). Expression of this reporter gene was dependent on the presence of estrogen or EDs in the culture medium. We found that the two-hybrid system with combination of the hER$\beta$ LBD and co-activator SRC-1 was most effective in the xenoestrogen-dependent induction of reporter activity. The extent of transcriptional activation by those chemicals correlated with their estrogenic activities measured by other assay systems, indicating that this assay system is efficient and reliable for measuring estrogenic activity. The data in this research demonstrated that the yeast detection system using steroid hormone receptor and co-activator is a useful tool for identifying chemicals that interact with steroid receptors.s.

• 한국환경보건학회지
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• 제29권2호
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• pp.7-15
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• 2003

DEHP는 대표적인 플라스틱 가소제 가운데 하나로서, 광범위하게 사용되고 있으며, 내분비계 장애물질로 분류퇴고 있다. 실제로 하천, 해양, 토양 등 광범위한 환경에서 검출되고 있지만, 이 물질이 수서 생물에 미치는 내분비교란 영향과 기작에 대해서는 거의 알려진 바가 없다. 본 연구에서는 송사리로 불리우는 Oryzias latipes(Japanese medaka)와, 유생 시기에 저니성 무척추 동물로 존재하다가 성충이 되는 Chironomus riparius를 대상으로 DEHP가 내분비 장애물질로서 생식작용에 미치는 영향에 대하여 연구하였다. 먼저, Japanese medaka를 부화 직후부터 3개월간 DEHP 1, 10, 50 $\mu\textrm{g}$/l의 농도로 노출시킨 결과 암놈의 혈중 비텔로제닌의 감소 ,생식소 지수인 GSI(Gonado Somatic Index) 감소. 난자 발달 저해 등이 관찰되었다. 또한, C. riparius를 산란 직후부터 DEHP에 노출시킨 경우에는 성체 출현률, 암수 비율, 산란률에서는 용량-반응 관계를 가진 변화가 발견되지 않았으나, 산란된 알의 부화율은 DEHP에 노출된 경우 유의하게 감소하는 것이 관찰되었다. 이러한 결과를 종합하여 볼 때. DEHP는 O. latpes와 C. riparius 모두 생식 작용에 영향을 미치며, 그 작용 기작은 일반적으로 발견되는 에스트로젠(estrogen) 활성이 아닌 암놈의 생식기관의 발달을 직, 간접적으로 저해함으로서 정상적인 알의 생성을 방해하는 이른바 항-에스트로젠 기작을 보이는 것으로 추정된다. 본 연구에서는 DEHP 위해성 평가를 위한 기본 자료로서, 생식작용 영향에 대한 새로운 자료를 제시하였다.

• 생약학회지
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• 제37권1호통권144호
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• pp.21-27
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• 2006

Yeast based estrogenicity assay is the simplest and useful for the assay and the discovery of novel estrogenic substances in natural specimens, The estrogen receptor(ER) modulation activity of 50% EtOH extracts of 101 traditional medicinal herbs was assessed using a recombinant yeast assay system with both a human estrogen receptor expression plasmid and a receptor plasmid. Among them, 14 species proved to be active. Pureariae Flos (flower of Puerraria thunbergiana BENTH.) had the highest estrogenic relative potency$(7.75{\times}10^{-3})$ $(EC_{50}=9.39\;{\mu}g/ml)$. The $EC_{50}$ value of $17{\beta}-estradiol$ used as the positive control was $0.073\;{\mu}g/ml)$ (Relative Potency=1.00). There results demonstrated that some of the traditional medical herb may be useful in the therapy of estrogen replacement.

• Environmental Analysis Health and Toxicology
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• 제20권1호
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• pp.13-21
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• 2005

The purpose of this study was to determine the effects of bisphenol A (BPA), which is known to have estrogenic activity, on the early development of medaka fish (Oryzias latipes). The fertilized eggs of medaka were treated with BPA at different concentrations for 3 weeks. Embryonic growth, deformation, hatching success, and gonadal differentiation were determined to observe the effects of this chemical. Also we tried to measure the estrogenic activity of bisphenol A using ELISA and RT-PCR methods. By using this techniques, we evaluated the induction of vitellogenin, an estrogen-regulated gene from the whole body-homogenates of larvae. At results, a reduced blood circulation was seen in embryos and peritoneal edema and hindrance of yolk-sac absorption were observed in larvae of treated group. However, BPA at the concentrations tested (2～200 ㎍/L) did not have severe adverse effects on the early life-stages. According to the observation of gonadal histology, inter-sex or sex -reversal was not found in all test fish. After the exposure was ended, vitellogenin mRNA and protein levels were measured in larvae and then their levels were found to be increased in treated group with 200㎍/L. These results indicate that BPA can induce the expression of vitellogenin in early life-stages as well as in adult male fish.

• 한국식품위생안전성학회지
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• 제21권4호
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• pp.197-203
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• 2006

Parabens are most wildly used in food, cosmetics and pharmaceutic products as preservatives caused of safety and cheap. we had examined that paraben had estrogenic activity through the in vivo and in vitro experiments in last year. We demonstrated that most of parabens(ethyl, butyl, propyl, isobutyl, isopropyl) increased significantly uterus weight as well as induced proliferation of MCF-7 cell and binding of estrogen receptor as endocrine disrupter compounds. In this study, we evaluated that whether parabens have effect on male reproductive system or not. the male rats were administrated parabens by oral injection then examined separation of preputial day for $PND23\simPND52$. As the results, most parabens delayed pubertal development compare to control group. The separation of preputial day of Butyl and Propyl parabens at high concentration were PND 44 days and PND 45days compared to control group as PND 40 days. Even though, parabens as endocrine disrupter wildly spread in food, cosmetics and pharmaceutic products, we didn't have the safe guideline. In abroad, they are re-evaluating safety assessment for parabens. In conclusion, parabens delayed pubertal development in juvenile parabens are consider as endocrine disrupter chemicals.