• Journal of Ginseng Research
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• 제24권1호
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• pp.8-17
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• 2000

스테로이드 호르몬의 일종인 에스트로젠은 생식기능에 영향을 미치는 것 외에 학습 및 기억과 관련된 기능에도 영향을 미치는 것으로 알려져 있다. 최근, 에스트로젠은 기억과 관련된 뇌세포 신 경망의 발달과 뇌 기능 장애를 방지할 수 있다는 부분에서 상당한 관심의 대상이되고 있다. 그러나 에스트로젠 대체 치료가 폐경기의 많은 여성들에게 도움을 주기도 하지만 여러 부작용을 유발하는 것으로도 알려져 있다 인삼 역시도 스테로이드 특성을 보이며 에스트로젠과 유사한 화학구조를 가지는 여러 성분을 가지고 있다. 본 실험의 목적은 첫째로 공간 기억력을 측정하기에 여러 장점을 가지고 있으면서 다른 어떠한 행동학적 실험보다 학습과 기억의 동물 모텔로 잘 알려진 방법인 Morris water maze를 이용하여 에스트로젠의 효과를 확인하고, 두 번째는 인삼이 학습과 기억에서 에스트로젠과 같은 효과를 나타낼 수 있는지를 확인하는 것이다. 본 실험은 인위적으로 난소를 제거한 쥐에 17$\beta$-estradiol(100~250 $\mu\textrm{g}$/ml), panaxadiol(PD), panaxatriol(PT) sapo-nins(15~100 $\mu\textrm{g}$/ml)을 sesame oil에 녹인 capsule을 implant했다. 첫 번째 실험에서 난소를 제거한 쥐에 에스트로젠을 투입했을때 학습과 기억의 효과를 확인했다. 두 번째 실험에서는 난소를 제거한 쥐에 3가지 다른 농도에서의 PD, PT를 투입했을 때 학습과 기억에 대한 에스트로젠의 효과와 비교해 보았다. 2주 동안의implant 후 water maze 실험결과 세 그룹 모두 난소를 제거한 그룹보다 기억력이 향상되었다 이러한 결과를 토대로 에스트로젠이 학습과 기억에 영향을 준다는 것을 확인할 수 있었고 PD, PT 또한 학습과 기억에 관련된 행동에서 에스트로젠과 같은 효과를 나타낼 수 있다는 것을 확인할 수 있었다. 이러한 동물모델에서의 연구를 통하여 인삼이 에스트로젠 장기결핍치료에서 나타나는 여러 호르몬 부작용을 극복할 수 있는 에스트로젠 대체물질로 개발되어 기억력 저하를 수반하는 Alzheimer's disease 및 여러 퇴행성 중추신경 질환의 치료제로 대체의학의 natural compound이용에 그 기초 기전을 제공할 수 있으리라 여긴다.

• 대한한방부인과학회지
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• 제30권2호
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• pp.16-36
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• 2017

목 적: 본 연구에서는 지백지황탕 열수추출물(수율=19.76%)의 갱년기 장애 개선 효과를 확인하기 위해 난소적출(Ovariectomy, OVX) 마우스 모델을 이용하여 estrogen 유사 효과, 항비만 효과, 고지혈증 억제 효과, 지방간에 대한 보호 효과 및 골다공증 억제 효과의 5가지 생리활성 효과로 구분하여 평가하였다. 방 법: 본 연구에서는 지백지황탕의 갱년기 장애 개선 효과를 평가하기 위해 사람의 다양한 갱년기 장애와 유사한 증상을 나타내는 난소적출 마우스모델을 활용하였다. 총 6개의 실험군에서 각 8마리의 마우스를 사용하여 위수술 sham 대조군, OVX 대조군, Estradiol 대조 약물군, 지백지황탕 500, 250, 125 mg/kg 투약 실험군으로 나누어 실험하였다. OVX 수술 28일 후부터 지백지황탕 추출물을 각각 500, 250 and 125 mg/kg으로 매일 1 회씩 84일 동안 경구투여하고, $17{\beta}$-estradiol $0.03{\mu}g/head/day$ 피하 투여군과 비교 하여 estrogen 유사 효과, 항비만 효과, 고지혈증 억제 효과, 지방간에 대한 보호 효과 및 골다공증 억제효과로 구분하여 평가 하였다. 본 실험결과는 $17{\beta}$-estradiol $0.03{\mu}g/head/day$ 피하 투여 마우스에서의 결과와 비교 평가 하였다. 결 과: 본 실험의 결과, OVX 대조군에서는 위수술 매체 대조군에 비해 현저한 체중 및 증체량, 체지방 및 복부 축적 지방량, 복부 축적 지방 중량, 혈청 중 AST, ALT, TC, LDL, TG 및 osteocalcin 함량의 증가가 자궁, 간 및 대퇴골 중량, 혈중 bALP 및 estradiol 함량, 평균 total body 골밀도 및 대퇴골 골밀도의 감소와 함께 인정되었으며, 현저한 복부 축적 지방 두께의 증가 및 지방세포의 비대, 간의 지방병증, 자궁의 불용성 위축, 대퇴골의 골량 감소 소견이 각각 인정되었다. 한편 이러한 OVX에 의해 유발된 estrogen 결핍성 폐경기 관련 갱년기 장애 소견이 지백지황탕 추출물 500, 250 및 125 mg/kg의 84일에 걸친 연속 투여에 의해 투여 용량 의존적으로 현저히 억제되었으며, 특히 지백지황탕 500 mg/kg은 estradiol $0.03{\mu}g/head/day$ 피하투여군과 유사한 갱년기 장애 개선 효과를 OVX 마우스에서 나타내었다. 결 론: 이상의 결과에서, 지백지황탕 500, 250 및 125 mg/kg의 경구투여는 OVX 마우스에서 estrogen 결핍성 폐경기 관련 갱년기 장애(비만, 고지혈증, 간 지방병증 및 골다공증) 개선 효과를 투여 용량 의존적으로 나타내었다. 그러나 지백지황탕은 총 8종의 약제로 구성되어 있고, 각각 수많은 생리활성 물질을 함유하고 있어, 향후 생리활성을 나타내는 화학성분의 검색과 더불어 다양한 방면으로 기전적인 연구가 체계적으로 수행되어야 할 것으로 판단된다.

• 한국발생생물학회지:발생과생식
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• 제17권3호
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• pp.289-297
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• 2013

Bisphenol A (BPA) is an estrogenic endocrine disrupter. However, depending on a way of treatment, the harmful effects of BPA have not been confirmed. Also, trans-generational effects of BPA on male reproduction are still controversial. Because the reabsorption of testicular fluid in the efferent ductules (ED) and initial segment (IS) is important for sperm maturation, the present study was designed to determine trans-generational effect of BPA administrated orally on expression of water transport-related molecules in the mouse ED and IS. Ethanol-dissolved BPA was diluted in water to be 100 ng (low), $10{\mu}g$ (medium), and $1mg/m{\ell}$ water (high). BPA-containing water was provided for two generations. Expression of ion transporters and water channels in the ED and IS were measured by relative real-time PCR analysis. In the ED, BPA treatment caused expressional increases of carbonic anhydrase II, cystic fibrosis transmembrane regulator, $Na^+/K^+$ ATPase ${\alpha}1$ subunit, and aquaporin (AQP) 1. No change of $Na^+/H^+$ exchange (NHE) 3 expression was detected. BPA treatment at medium dose resulted in an increase of AQP9 expression. In the IS, the highest expressional levels of all molecules tested were observed in medium-dose BPA treatment. Generally, high-dose BPA treatment resulted in a decrease or no change of gene expression. Fluctuation of NHE3 gene expression by BPA treatment at different concentrations was detected. These findings suggest that trans-generational exposure to BPA, even at low dose, could affect gene expression of water-transport related molecules. However, such effects of BPA would be differentially occurred in the ED and IS.

• 한국발생생물학회지:발생과생식
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• 제15권3호
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• pp.223-230
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• 2011

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental contaminants derived from incomplete combustion of carbons and crude oil. In this study, we investigated the effects of benzo[a]pyrene (B[a]P), a representative PAHs on in vitro sex steroid hormone production and germinal vesicle breakdown (GVBD) using isolated oocytes of longchin goby (Chasmichthys dolichognathus) and chameleon goby (Tridentiger trigonocephalus). Oocytes in diameters of 0.8-0.9 (end vitellogenic stage) and 0.9-1.0 mm (germinal vesicle migratory stage) from longchin goby and 0.5 mm (fully vitellogenic stage) from chameleon goby were used. In GVBD assay, B[a]P at 10 nM stimulated GVBD in the oocytes of 0.8-0.9 mm from longchin goby. B[a]P at 1 nM stimulated GVBD in the oocytes with diameter 0.5 mm from chameleon goby. In steroid production from oocytes of longchin goby, B[a]P at 100 nM decreased testosterone (T) production, B[a]P at 1,000 nM increased estraiol-17 (J (E2) production and 10 and 100 nM increased $17,20{\beta}$-dihydroxy-4-pregnen-3-one ($17{\alpha}20{\beta}P$) production in the oocytes with diameter 0.8-0.9 mm. B[a]P at 1,000 nM increased E2 production, 100 and 1,000 nM increased $17{\alpha}20{\beta}P$ production in the oocytes with diameter 0.9-1.0 mm. In steroid production of oocytes from chameleon goby, B[a]P at 1,000 nM increased $E_2$ production. B[a]P at 10 nM increased $17{\alpha}20{\beta}P$ production. In the ratio of $E_2$ to T ($E_2$/T), B[a]P at 100 and 1,000 nM increased $E_2$/T in the oocytes of longchin goby. B[a]P at 100 nM also increased $E_2$/T in the oocytes of chameleon goby. Taken together, these results suggest that B[a]P have not only weak estrogenic effects but progestogenic effects on oocyte maturation.

• 한국환경보건학회지
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• 제29권4호
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• pp.27-34
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• 2003

Bisphenol A is used in the manufacture of epoxy, polycarbonate, and corrosion-resistant unsaturated polyester-styrene resins required for food packaging materials in industrial processing. Some reports indicated the possibility of harmful effects on rats. In this study was used a method for the determination of bisphenol A in blood according to the OSHA High Performance Liquid Chromatography (HPLC) guideline. The method involved blood extraction using methylene chloride. And it was evaluated developmental and teratogenic effects in pregnant rats and second generation. The results obtained were as follows. There was a significant increase in the body weights and treated groups F1 female in liver, spleen, kidney, but according to dose-response. F1 female rat's relative body weight and absolute body weight are not different. There was a significant increase liver, spleen, kidney organ weight and reproductive organ weight epididymis, prostate gland in F1 male rats. There was a proestrous in pregnant rat, group 200 $\mu\textrm{g}$/kg, 2000 $\mu\textrm{g}$/kg, 20,000 $\mu\textrm{g}$/kg. The effect on rat treated with bisphenol A decrease organ weight and reproductive organ weight. Identification and quantitation were performed with using HPLC C18 column and using at retention time 5.5 min. The results of the detection of bisphenol A were at 20,000 $\mu\textrm{g}$/kg in average 1 $\mu\textrm{g}$/ml, 200 $\mu\textrm{g}$/kg average in 0.9 $\mu\textrm{g}$/ml blood samples. From those results, it could be concluded that the effects of pregnant rat and second generation(F1) by bisphenol A treatment during lactational period were estrogenic and bisphenol A was remained in serum at low level.

• 한국환경보건학회:학술대회논문집
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• 한국환경보건학회 2003년도 Challenges and Achievements in Environmental Health
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• pp.171-173
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• 2003

Bisphenol A (4,4'-isopropylidenediphenol, C$\_$15/H$\_$16/O$_2$) is the monomer used in the manufacture of polycarbonate. Polycarbonate, in turn, is used in a wide array of plastic products, with new applications continuously being developed. Also it has been used to produce epoxy resins and polycarbonate plastics for food container. This study was carried out to investigate the effects of bisphenol A on lactation period to dams and F1, Sprague-Dawley females were mated with on 2:1 ratio basis. Various doses of bisphenol A (0, 2, 20, 200, and 2,000 $\mu\textrm{g}$/kg) were daily administered to females for 21 days after parturition. Dams and offsprings were sacrificed at the time of weaning. The results were as follows, 2000 $\mu\textrm{g}$/kg of bisphenol A decreased the dams' body weight at post-partum 18 days and also 200 and 2000 $\mu\textrm{g}$/kg of bisphenol A decreased the body weight of neonates at the days of post-partum 21 days. Bisphenol A increased the relative weights of liver and spleen in male offsprings, depending on the doses. But female offsprings showed high relative organ weights of ovaries, and low relative organ weights of uterine in a some dose-response manners. High dose of bisphenol A induced low viability of neonates exposed during lactation period. The dams treated with bisphenol A showed prematured estrous stage. Bisphenol A was recovered about 21.2% average in serum of dams, and also in offsprings'. The results indicate that the bisphenol A induces estrous cycle during lactation period in dams, also reaches to the of offspring through breast milk. Thus bisphenol A exopsed to dams and neonates via lactation induces some estrogenic and toxic effects.

• 환경생물
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• 제21권2호
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• pp.208-215
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• 2003

Bisphenol A (4,4'-isopropylidenediphenol, $C^{15}H_{16}O_{2}$) is the monomer used in the manufacture of polycarbonate. Polycarbonate, in turn, is used in a wide array of plastic products, with new applications continuously being developed. Also it has been used to produce epoxy resins and polycarbonate plastics for food container. This study was carried out to investigate the effects of bisphenol A on lactation period to dams and F1. Sprague-Dawley females were mated with on 2 : 1 ratio basis. Various doses of bisphenol A (0, 2, 20, 200, and 2,000 ${\mu}g kg^{-1}$) were daily administered to females for 21 days after parturition. Dams and offsprings were sacrificed at the time of weaning. The results were as fellows, 2000 ${\mu}g \; kg^{-1}$ / of bisphenol A decreased the dams' body weight at post-partum 18 days and also 200 and 2,000 ${\mu}g \;kg^{-1}$ of bisphenol A decreased the body weight of neonates at the days of post-partum 21 days. Bisphenol A increased the relative weights of liver and spleen in male offsprings, depending on the doses. But female offsprings showed high relative organ weights of ovaries, and low relative organ weights of uterine in a some dose-response manners. High dose of bisphenol A induced low viability of neonates exposed during lactation period. The dams treated with bisphenol A showed prematured estrous stage. Bisphenol A was recovered about 21.2% average in serum of dams, and also in offsprings'. The results indicate that the bisphenol A induces estrous cycle during lactation period in dams, also reaches to the offspring through breast milk. Thus bisphenol A exopsed to dams and neonates via lactation induces some estrogenic and tonic effects.

• 동의생리병리학회지
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• 제24권2호
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• pp.220-227
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• 2010

Puerariae radix (PR) is a popular natural herb and a traditional food in Asia, which has antithrombotic and anti-allergic properties and stimulates estrogenic activity. One of the major side effects of cisplatin is nephrotoxicity, leading to acute renal failure. Recent study has suggested a role of ROS and p53 in renal cell injury by cisplatin. We studied that protective effects of PR on cisplatin-induced apoptosis in rat mesangial cell. Rat mesangial cell was preincubated with PR (50, 100, 150 and 200 ${\mu}g/m{\ell}$) for 12 hr and then treated with 30 ${\mu}M$ cisplatin for 24 hr. Protective effect of PR on cisplatin-induced apoptosis in ECV304 cells was determined using MTT assay, FDA-PI staining, flow cytometric analysis, caspase-3 activity assay, ROS assay and western blot. Our results showed that PR inhibited in cisplatin-induced apoptosis and ROS production in ECV304 cells. Moreover, PR reduced ERK, p38 and JNK activation that increased in cisplatin-treated rat mesangial cell. Furthermore, activation of p53 by cisplatin in rat mesangial cell was inhibited by PR treatment. These results suggest that protective effect of PR on cisplatin-induced apoptosis in rat mesangial cell may be associated with reduction of ERK, p38, JNK, p53 activation.

• Clinical and Experimental Reproductive Medicine
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• 제40권2호
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• pp.60-66
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• 2013

Objective: Impairment of spermatogenesis has been identified as an inevitable side effect of cancer treatment. Although estrogen treatment stimulates spermatogenic recovery from the impaired spermatogenesis by suppressing the intra-testicular testosterone (ITT) level, side effects of estrogen are still major impediments to its clinical application in humans. Soybeans are rich in genistein, which is a phytoestrogen that binds to estrogen receptors and has an estrogenic effect. We investigated the effects of genistein administration on ITT levels, testis weight, and recovery of spermatogenesis in rats treated with a chemotherapeutic agent, busulfan. Methods: Busulfan was administered intraperitoneally to rats, and then a GnRH agonist was injected subcutaneously into the back, or genistein was administered orally. Results: The weight of the testes was significantly reduced by the treatment with busulfan. The testis weight was partially restored after busulfan treatment by additional treatment with either the GnRH agonist or genistein. Busulfan also induced atrophy of a high percentage of the seminiferous tubules, but this percentage was decreased by additional treatment with either the GnRH agonist or genistein. Treatment with genistein was effective at suppressing and maintaining ITT levels comparable to that in the GnRH agonist group. Conclusion: Genistein effectively suppressed ITT levels and stimulated the recovery of spermatogenesis in rats treated with a chemotherapeutic drug. This suggests that genistein may be a substitute for estrogens, for helping humans to recover fertility after cancer therapy without the risk of side effects.

• Toxicological Research
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• 제16권1호
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• pp.27-31
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• 2000

Recently, there is a worldwide concern that a great number of man-made chemicals have a hormone-like action both in humans and in animals. EPA and OECD are developing screening programs using validated test systems to determine whether certain substances may have an effect on humans. In the present study, the establishment of in vivo short-term test system for pubertal female assay with thyroid to detect endocrine disrupting chemicals was tried using a model substance, methoxychlor (MC), a chlorinated hydrocarbon insencticide. Forty female rats were assigned to four groups. MC was administered at dose levels of 0, 8, 40 and 200mg/kg by gavage to female rats from day 21 post partum to the completion of vaginal opening. We evaluated body weight change, age at vaginal opening, onset of estrous cyclicity, age at first esturs, ovary weight, and serum concentrations of thyroxine and thyroid stimulating hormone in female rats. The age at vaginal opening of females receiving 40 200mg/kg was significantly younger than control. The onset of estrus cyclicity and age at first estrus of females receiving 200mg/kg was also younger than controls. There was no effect of treatment on body weight, ovary weight, and hormone concentration. Based on these results, it can be concluded that application of MC at dose level of 40mg/kg affects the vaginal opening and application of MC at dose level of 200mg/kg accelerates the vaginal opening and the onset of estrus cylicity.