• Proceedings of the Korea Society of Environmental Toocicology Conference
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• 한국환경독성학회 2002년도 추계국제학술대회
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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.

• Applied Microscopy
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• 제14권2호
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• pp.29-37
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• 1984

Morphological changes of the epithelium of the endometrium by prolonged treatment of $17{\beta}$-estradiol or progesterone in ovariectomized rats was studied at the ultrastructural level. The epithelium of the endometrium in ovariectomized rats was characterized by the appearance of a number of vacuoles which was contained with the membraneous structures, lipid droplets and the others. The epithelium was low cuboidal, and a few short microvilli were present at the cell surface. Secretory granules are rarely found. After estradiol treatment, the epithelium was high columnar in shape. The mitochondria was appeared throughout the cytoplasm, however, long or swelling mitochondria was often found. Golgi apparatus and rER were relatively well-developed. Relatively long and sparse microvilli were present at the cell surface. After progesterone treatment, the epithelium was characterized by the appearance of numerous vesicles at the apical region and numerous lipid droplets at the subnuclear region. At the cell surface a number of short and blunt microvilli were found. These data indicated that the endometrium was dependent on estrogen and progesterone for changes in both its morphological and functional state and suggested that each hormone exerted a unique effect on the epithelial cells.

• Proceedings of the Korean Society of Embryo Transfer Conference
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• 한국수정란이식학회 2002년도 국제심포지엄
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• pp.114-114
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• 2002

포유동물에서 뇌와 부신에서 합성.분비되는 카테콜아민(Catecholamine, CA)계 신경전달물질인 dopamine(DA), norepinephrine(NE), epinephrine(E)은 체내 각종 생리현상의 조절에 필수적이며, 생식과 관련지어서는 시상하부-뇌하수체 간 GnRH-gonadotropin 호르몬 축의 활성을 조절하는 기능 외에도 번식과 관련된 여러 행동양식을 조절함이 잘 알려져 있다. 본 연구는 CA 생합성 효소들인 tyrosine hydroxylase(TH), dopamine beta-hydroxylase(DBH), phenylethanolamine-N-methyltransferase(PNMT)의 유전자 발현에 미치는 sex steroid의 영향을 조사하였다. 성숙한 암컷 횐쥐(SD strain)의 난소를 제거하고 1주 경과 후 vehicle(sesame oil; OVX+Oil 실험군) 또는 estradiol 17$\beta$(235ug/m1; OVX+E$_2$실험군)이 든 silastic capsule(길이 14mm; 내경 1.55mm; 외경 3.125mm)을 48 시간 동안 처리한 뒤 희생시켰다. 적출된 조직으로부터 RNA를 추출한 후 semi-quantitative RT-PCR을 시행하였다. (i) TH의 발현 정도는 OVX+Oil 군에서는 시상하부) substantia nigra(SNc)) 부신 순으로, OVX+E$_2$군에서는 SN글 부신) 시상하부 순으로 나타났다. TH 발현에 미치는 estradiol의 효과로 SNc과 부신에서는 유의한 증가를 보인데 비해 시상하부에서는 유의한 감소를 관찰하였다. (ii) DBH 발현 정도는 OVX+Oil군에서는 SNc> 부신> 시상 하부 순으로, OVX+E$_2$군에서는 부신＞ SNc＞ 시상하부 순이었다. DBH 발현에 미치는 estradiol의 효과로 SNc에서는 유의한 감소, 부신에서는 유의한 증가, 그리고 시상하부에서는 통계적 유의성은 없으나 감소하는 경향을 보였다. (iii) PNMT의 발현의 경우 SNc와 시상하부에서는 기보고된 바와 같이 alternative splicing에 의해 110bp 차이의 크고 작은 두 형태의 cDNA(PNMTI & PNMTs)가 증폭되었으나 부신에서는 작은 cDNA 만이 관찰되었다. PNMTs의 발현 정도는 OVX+Oil군과 OVX+E$_2$군에서 공히 부신＞ 시상하부＞ SNc 순이었고, PNMTI의 발현은 SNc가 시상하부 보다 다소 높은 경향이었으나 유의성은 없었다. PNMTs 발현에 미치는 estradiol의 효과로 SNc에서는 유의한 감소, 부신에서는 유의한 증가, 그리고 시상하부에서는 통계적 유의성은 없으나 증가하는 경향을 보였다. 본 연구에서는 CA 생합성 효소들의 유전자 발현의 조절에 미치는 estrogen 의 영향이 세포 기원이 neural crest cell인 부신 수질은 물론 뇌의 상이한 지역간에서도 조직특이적임을 관찰하였다. 이러한 결과는 각 조직에서의 estrogen 수용체 유형의 차이 혹은 작용 모드와 각 효소 유전자 발현 사이에 중요한 상관관계가 있음을 시사한다.

• Proceedings of the KSAR Conference
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• 한국동물번식학회 2004년도 춘계학술발표대회
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• pp.240-240
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• 2004

The modification of in vitro maturation (IVM) conditions should be required to efficient production of matured porcine oocyte in vitro. Estradiol-17β (E₂) as steroid hormone exists in ovarian follicular fluid and plays a major role in ovulation. It has been reported that estradiol as well as other steroids are involved in keeping the oocytes in meiotic arrest. (omitted)

• Journal of Life Science
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• 제19권12호
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• pp.1851-1854
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• 2009

This study correlated changes in the plasma levels of estradiol-$17{\beta}$ (E2) with changes in the gonadosomatic index (GSI) and ovarian development during the annual reproductive cycle of the pike eel Muraenesox cinereus, collected at the Tongyung coast region. Ovarian maturity was classified based on histological observations; the perinucleolus stage (November to February), the oil droplet stage (March to April), the early vitellogenic stage (April to May) and the late vitellogenic stage (June to October). Seasonal changes in the GSI were correlated with water temperature and reflected the degree of ovarian maturity. Plasma E2 levels were correlated with changes in the GSI, which increased from April to a peak in July, and the levels remained comparatively high until October. These data indicated that changes in the GSI and plasma E2 levels are correlated with the annual ovarian activity of the pike eel. In this study, however, female pike eels were not collected during the spawning stage. Therefore, spawning of this species seemed to be closely related to its migration toward the deep sea of offshore.

• Journal of Life Science
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• 제23권8호
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• pp.998-1003
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• 2013

The effects of oral administration of estradiol-$17{\beta}$ (E2) on glass eels (Body weight: $0.16{\pm}0.05g$, Total length: $6.2{\pm}0.9cm$) and young eels (Body weight: $2.6{\pm}0.6g$, Total length: $13.2{\pm}0.6cm$) on gonadal sex and growth were examined, respectively. Glass eels were fed a diet containing E2 at a dose of 10 mg/kg or 25 mg/kg, respectively, for five months. The female ratio significantly increased in all E2-treated groups (10 mg/kg diet group: 70%; 25 mg/kg diet group: 90%) when compared to the control group (10%). Young eels were fed a diet containing E2 at a dose of 25 mg/kg for four months. The female ratio also significantly increased in the E2-treated groups (60%) compared to the control group (20%). The highest female ratio was observed in the stage of glass eels rather than young eels. In all experiments, however, the growth of eels treated with E2 was similar to that of controls to the end of the experiment. Thus, oral administration of E2 could be a good approach to controlling sex differentiation.

• Journal of Environmental Health Sciences
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• 제31권3호
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• pp.227-233
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• 2005

This study was conducted to determine the endorcrine disruption effects of the several major pharmaceutical residues in water using adult Japanese medaka (Oryzias latipes). Four frequently used pharmaceuticals including caffeine, ketoconazole, acetaminophen, and diltiazem were investigated for the vitellogenin(Vtg) induction in the medaka using Western blotting and ELISA. $17\beta$,-estradiol was used as a positive control. Vtg was qualified and quantified through Western blot and ELISA. Following SDS gel electrophoresis, the dominant protein band was identified to molecular weight approximately 205 kDa in whole body samples of vitellogenic female. With female medaka exposed to $17\beta,-estradiol$, no significant difference in total protein induction was noted. In contrast, three to five day exposure of male fish to $17\beta,-estradiol$ resulted in $63.07\%o$, increase of total protein comparing to that of control males (p<0.01). Vtg induction in male fish was observed with all the test pharmaceuticals: At concentrations greater than 1ppm of diltiazem, 2 ppm of caffeine, 4 ppm of acetaminophen, and 10 ppm of ketoconazole, Vtg induction was monotonously increased in a dose dependent manner. This study is one of the first reports suggesting potential endocrine disruption mechanism of common human pharmaceutical products in aquatic ecosystem. Although the effect concentrations obtained from this investigation are environmentally unrealistically high, endocrine disruption should be considered as one of the important consequences of pharmaceutical pollution in aquatic environment, and warrants due attention in future researches.

• Journal of Environmental Health Sciences
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• 제32권3호
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• pp.227-234
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• 2006

There has been increasing concern in recent years about the occurrence, fate and toxicity of pharmaceutical products in aquatic environment. Although these compounds have been detected in a wide variety of environmental samples including sewage effluent, surface waters, ground water and drinking water, their concentrations generally range from the low ppt to ppb levels. It is therefore often thought to be unlikely that pharmaceuticals will have a detrimental effect on the environment. This study was conducted to determine the endocrine disruption effects of the several pharmaceutical residues in water using adult Japanese medaka (Oryzias latipes). The common antibiotics were used sulfa durgs (sulfamethoxazole and sulfamethazine) and tetracycline drugs (oxytetracycline and tetracycline). Positive control that was induced Vtg (vitellogenin) in male fish was used $17\beta$-estradiol. Vtg was qualified and quantified through Western blotting and ELISA. After SDS gel electrophoresis, the dominant protein band was identified to molecular weight approximately 205 kDa in whole body samples of vitellogenic female. In female medaka exposed to $17\beta$estradiol, there was no significant difference in total protein induction. In contrast, three to five day exposure of male fish to $17\beta$-estradiol resulted in more than 60.0% increase of total protein compared to that of control males (p<0.01). In case of antibiotics, female fish didn't show significant difference, but male fish was showed significant difference. In addition, Vtg induction in male fish was observed with all the test chemicals. On concentrations greater than 0.1 ppm of sulfamethoxazole, 1 ppm of sulfamethazine, 1 ppm of oxytetracycline and 20 ppm of tetracycline, Vtg induction was increased in a dose response manner. This study is one of the early reports suggesting potential endocrine disruption mechanism of antibiotic pharmaceutical products in aquatic ecosystem. Although the effect concentrations obtained from this study were high as unrealistically as in environments, it is endocrine disruption that we should be considered as one of the important consequences of pharmaceutical contamination at water environment, and warrants due attention in future researches.

• Nutrition Research and Practice
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• 제8권5호
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• pp.539-543
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• 2014

BACKGROUND/OBJECTIVES: Soy isoflavones are structurally similar to estrogen and bind to estrogen receptors, suggesting that they exhibit estrogenic activities; therefore, they are referred to as phytoestrogens. Fermentation may affect the bioavailability of isoflavones altering soy isoflavone glycosides in the form of aglycones. Thus, this study investigated the effects of fermented soybeans by Rhizopus oligosporus on bone metabolism in both young rats as a pilot test and in ovariectomized (ovx) old rats as a model of menopause. MATERIALS/METHODS: In the pilot test, a total of 24 seven-week-old female Sprague-Dawley (SD) rats were fed one of three diets for a period of four weeks: casein, unfermented soybean product, or fermented soybean product by R. oligosporus. In the ovx rat model, 20-week-old SD rats weighing 260-290 g underwent either sham-operation (n = 10) or bilateral ovariectomy (n = 30) and were then fed the AIN-93M diet for one week. Thereafter, rats were fed sham-casein, ovx-casein, ovx-soybean, or ovx-fermented soybean diet for five weeks. After decapitation, femoral bones were isolated and preserved in 9% formalin for assessment of bone mineral density (BMD), bone mineral content (BMC), and bone-breaking strength (BBS). RESULTS: Ovx rats showed significantly increased weight gain and decreased uterine wet weight. Of particular interest, ovx rats fed fermented soybeans showed increased uterine wet weights compared to control rats. Fermented soybean diet caused a significant increase in plasma 17-${\beta}$ estradiol concentrations in young rats, and 17-${\beta}$ estradiol levels were enhanced in ovx rats to match those of sham-operated ones. Significantly lower femoral BMD and BMC were observed in ovx rats compared to sham-operated controls, whereas bone areas did not differ statistically among the groups. In addition, BBS tended to be increased in ovx rats fed soybeans and fermented soybeans. CONCLUSIONS: Supplementation of fermented soybeans could have preventive and therapeutic effects against osteoporosis in postmenopausal women.

• Journal of Aquaculture
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• 제11권2호
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• pp.241-248
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• 1998

Effects of A23187 on estradiol$-17^{\beta}$-induced vitellogenin (VTG) induction were electrophore-tically examined in primary hepatocyte cultures in rainbow trout. hepatocytes were predultured for 2 days and then estradiol-$17^{\beta}$(E2, $2{\times}10^{-6}$M) and calcium ionophore (A23187, $10^{-7)$~$10^{-5}$ M) were added to the incubation medium. The hepatocytes were cultured for 7 more days. In addition, effects of A23187 on $E_2$-primed VTG production were investigated for 7 days. The addition of A23187 ($10^{-7)$~$10^{-5}$M) to the incubation medium specifically reduced VTG production by hepatocytes in a concentration-dependent way. The addition of A23187 significantly reduced the rate of $E_2$-primed VTG production to 18% of the control (E2 only) on Day 7. However, $E_2$-primed VTG production was reduced to 47% of the control by withdrawal of $E_2$ from the incubation medium. Therefore, these results suggest that intracellualr sequestered calcium could regulate VTG synthesis at the translational and/or post-translational stage.