• Asian-Australasian Journal of Animal Sciences
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• 제21권4호
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• pp.510-522
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• 2008

Our earlier studies showed that estrogen was involved in the regulation of fluid reabsorption in adult mouse efferent ductules (ED), through estrogen receptor (ER) ${\alpha}$ and $ER{\beta}$ by modulating gene expression of epithelial genes involved in ion homeostasis. However, little is known about the importance of $ER{\alpha}$ in the ED during postnatal development. Based on previous findings, we hypothesized that there should be a difference in the expression of epithelial ion transporters and anion producers in the ED of postnatal wild type (WT) and estrogen receptor ${\alpha}$ knockout (${\alpha}ERKO$) mice. Using absolute, comparative and semi-quantitative RT-PCR along with immunohistochemistry, we looked at expression levels of several genes in the ED across postnatal development. The presence of estrogen in the testicular fluid was indirectly ascertained by immunohistochemical detection of the P450 aromatase in the testis. There was no immunohistochemically detectable difference in the expression of P450 aromatase in the testes and ER${\beta}$ in the ED of WT and ${\alpha}$ERKO mice. ER${\alpha}$ was only detected in the ED of WT mice. The absence of ER${\alpha}$ in the ED of postnatally developing mice resulted in differential expression of mRNAs and/or proteins for carbonic anhydrase II, $Na^+/H^+$ exchanger 3, down-regulated in adenoma, cystic fibrosis transmembrane regulator, and $Na^+/K^+$ ATPase ${\alpha}$. Our data indicate that the absence of ER${\alpha}$ resulted in altered expression of an epithelial ion producer and transporters during postnatal development of mice. We conclude that the presence of ER${\alpha}$is important for regulation of the ED function during the prepubertal developmental and postpubertal period.

• Toxicological Research
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• 제33권1호
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• pp.71-77
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• 2017

Hormone replacement therapy (HRT) consists of highly effective prescription medications for treating menopausal symptoms; however, these agents have exhibited side effects including the risk of estrogen-induced carcinogenesis. Therefore, interest in phytotherapy-based materials as a natural source of alternatives to estrogen therapy has increased. However, some of these herbal medicines have been reported to increase the risk of estrogen-induced cancer. Herbal formulations composed of a combination of Cynanchum wilfordii Hemsley (CW), Phlomis umbrosa Turczaninow (PU), and Angelica gigas Nakai (AG) extracts (CPAE) have been used for treating menopausal symptoms. Therefore, in this study, we aimed to examine the safety of CPAE by determining its potential adverse estrogenic activity using the Organization for Economic Cooperation and Development (OECD) test guideline 455 (TG455) in a stably transfected transcriptionally activated human estrogen receptor ${\alpha}$ ($hER{\alpha}$)-HeLa9903 cell model. We found that CPAE did not how any estrogenic activity or stimulate promoters containing estrogen response elements in MCF-7 cells. In addition, CPAE showed no significant selective activity against $hER{\alpha}$ and $hER{\beta}$, non-selective activity against the ER, or effects on ER target gene expression. Furthermore, CPAE did not significantly induce MCF-7 cell proliferation and uterine weight increase in ovariectomized rats. These results demonstrate that CPAE can be used as beneficial herbal drug for prevention and therapeutic intervention of estrogen carcinogenesis in menopausal women.

• 여성건강간호학회지
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• 제8권2호
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• pp.151-164
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• 2002

PURPOSE: Estrogen replacement therapy is indicated for the relief of hot flushes and urogenital atrophy, the prevention of osteoporosis and the reduction in risk of cardiovascular disease. The present study assessed by blood pressure, heart rate variability, and climacteric symptoms in menopausal women before treatment and at 1 month during estrogen replacement therapy. METHODS: The study sample consisted of 16 healthy menopausal women (range 49 to 59 years, mean : 53.4 years) attending menopausal clinics for the complaint of climateric symptoms at S. hospital in Chunchoen. They were all non-smokers and no patient had symptoms or evidence of cardiovascular disease. They took estrogen replacement therapy (conjugated estrogen 0.625 mg with or without medroxy progesteron 2.5mg) for 1 month. Blood pressure, heart rate variability(heart period and vagal tone) through ECG, and climacteric symptom were measured in all subjects before treatment and at 1 month during treatment. Climacteric symptom questionnaire which was developed by Neugarten et al.(1963) was modified with 20 items of question(Cronbach's alpha = 88 -.89). The data was collected from Sept. 1. 2000 to July. 30. 2001. RESULTS: There was no significant difference in mean systolic and diastolic pressure between the baseline and at 1 month during treatment. The mean heart period and vagal tone were slightly increased, but difference of mean heart period and vagal tone were not statistically significant between the baseline and at 1 month during treatment. The score of climacteric symptoms decreased significantly from the baseline after treatment. CONCLUSIONS: Even though, this study did not show that estrogen replacement therapy led decrease of blood pressure and increase heart rate variability, climacteric symptoms reduced much in all subjects after taking drugs. These results suggest that there is need to repeat study with long term period.

• Molecules and Cells
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• 제28권1호
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• pp.67-71
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• 2009

Estrogen receptor ${\alpha}$ ($ER{\alpha}$) mediates the mitogenic effects of estrogen. $ER{\alpha}$ signaling regulates the normal growth and differentiation of mammary tissue, but uncontrolled $ER{\alpha}$ activation increases the risk to breast cancer. Estrogen binding induces ligand-dependent $ER{\alpha}$ activation, thereby facilitating $ER{\alpha}$ dimerization, promoter binding and coactivator recruitment. $ER{\alpha}$ can also be activated in a ligand-independent manner by many signaling pathways, including protein kinase A (PKA) signaling. However, in several $ER{\alpha}$-positive breast cancer cells, PKA inhibits estrogen-dependent cell growth. FoxH1 represses the transcriptional activities of estrogen receptors and androgen receptors (AR). Interestingly, FoxH1 has been found to inhibit the PKA-induced and ligand-induced activation of AR. In the present study, we examined the effects of PKA activation on the ability of FoxH1 to represses $ER{\alpha}$ transcriptional activity. We found that PKA increases the protein stability of FoxH1, and that FoxH1 inhibits PKA-induced and estradiol-induced activation of an estrogen response element (ERE). Furthermore, in MCF7 cells, FoxH1 knockdown increased the PKA-induced and estradiol-induced activation of the ERE. These results suggest that PKA can negatively regulate $ER{\alpha}$, at least in part, through FoxH1.

• 한방재활의학과학회지
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• 제30권1호
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• pp.1-12
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• 2020

Objectives Depletion of ovarian function after menopause in women induces estrogen deficiency leading to increased fat and decreased muscle mass. In this study, we examined the effect of herbal medicines by measuring hormone expression in muscle tissue of estrogen-deficient rats induced by ovariectomy. Methods Ovariectomy was performed to induce estrogen deficiency, and mice were given herbal prescription (HP) for 6 weeks. Estrogen-deficient rats were divided into two groups: one group (HPH) which were orally administered HP 200 mg/kg and the other group (HPL) administered HP 40 mg/kg. Weight changes in both groups were measured using polymerase chain reaction (PCR). After extraction of the femoral muscles in mice, the expression of the leptin, lipoprotein lipase (LPL), diacyl glycerol acyltransferase (DGAT)1, peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α, NADH dehydrogenase (NDH), farnesyl diphosphate farnesyltransferase (FDFT)1, lanosterol synthase (LSS), phosphatidylethanolamine N-methyltransferase (PEMT), and peroxiredoxin (Prdx6) were measured using PCR. Results HP increased the expression of leptin, LPL, DGAT1, PGC-1α, NDH, FDFT1, LSS, PEMT, and Prdx6. HP affects body fat metabolism and is effective in improving menopausal obesity and obesity complications caused by estrogen deficiency. However, HP does not affect the expression of tumor necrosis factor-α and 3-hydroxy-3-methylglutaryl-CoA reductase, and thus will not be effective in obesity-related metabolic diseases. Conclusions HP is thought to inhibit weight gain by regulating hormone expression related to glucose metabolism and lipid metabolism in muscle tissue of estrogen-deficient rats.

• 농업과학연구
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• 제3권1호
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• pp.61-65
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• 1976

가토(家兎)의 과배란유기(過排卵誘起)에 있어 P.M.S. 처리(處理)에 의(依)한 Estrogen의 병용효과(倂用效果)를 시험(試驗)하기 위(爲)해, P.M.S. 40I.U를 5일간(日間) 처리(處理)한것과, P.M.S.G. 40IU를 5일간(日間) 처리(處理)하고 최종일(最終日)에 Estrogen 0.1~0.5mg을 병용주사(倂用注射)한 것의 난소소견(卵巢所見)을 비교(比校)하며 배란수(排卵數)를 계측(計測)한 결과(結果), 다음과 같이 그 결과(結果)를 요약(要約)하였다. 1. P.M.S. 40IU를 5일간(日間) 피하주사(皮下注射)하여 24시간(時間) 및 48시간후(時間後)에 교미자극(交尾刺戟)을 준 대조구(對照區)의 평균(平均) 배란수(排卵數)는 21.3~24.1개(個), 과배란(過排卵) 양성률(陽性率) 50~63%에 비(比)하여 P.M.S.G 40, IU를 주사(注射)하고 최종일(最終日)에 Estrogen 0.1~0.5mg을 병용처리(倂用處理)한 구(區)의 평균(平均) 배란수(排卵數)는 32.5~37.8개과배란(個過排卵) 양성률(陽性率)은 87.5~100%로서 Estrogen을 병용처리(倂用處理)한 것이 배란수(排卵數)가 높아지는 경향(傾向)을 나타냈으며 미피열배란수(未破裂排卵數)는 대조구(對照區)가 많은 반면(反面), Estrogen 병용구(倂用區)는 적은 경향(傾向)을 나타냈다. 2. 대조구(對照區)와 Estrogen 병용구(倂用區)에 대(對)하여 난포(卵胞)를 1.0~1.4mm, 1.5~2.4mm, 2.5mm 이상(以上)의 3종(種)으로 분류(分類)한 후(後) 경시적(經時的) 관찰(觀察)에 의(依)한 발육정도(發育程度)를 비교(比較)한 결과(結果) 3종(種)에 대(對)한 배란수(排卵數)의 추이(推移)는 양구(兩區)가 서로 틀려서 총배란수면(總排卵數面)은 Estrogen 병용구(倂用區)가 우수(優秀)하였다 3. 이런 결과(結果)로 미루어 볼때 P.M.S. 주사(注射)에 대(對)한 Estrogen의 병용처리(倂用處理)는 외면적(外面的)으로는 난포발육(卵胞發育)에 대(對)하여 직접(直接) 영향(影響)을 주지 않으나 미피열난포(未破裂卵胞)를 줄여 배란수(排卵數)를 증가(增加)시키는 경향(傾向)을 나타냈다.

• 생명과학회지
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• 제13권3호
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• pp.314-323
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• 2003

지금까지 estrogen 호르몬이 유방암의 발생과 진전에 관여한다는 사실을 뒷받침 할 수 있는 여러 가지 증거가 제시되어 왔지만, 암화에 관여하고 있는 estrogen의 분자생물학적 작용기전에 대해서는 아직 명확히 알려져 있지 않다. 유방암 세포의 발암현상은 다양한 핵 수용체들과 이들 각각의 신호전달경로들 사이의 기능적 상호교류 (Functional Cross-talk)에 의해 조절되는 것으로 추측되고 있다. 그러므로, 유방암세포의 성장과 증식에 관여하는 신호전달경로중에서 estrogen의 작용을 조절할 수 있는 핵 수용체를 밝혀내고, 이러한 수용체와 estrogen receptor사이에 어떠한 기능적 상호교류가 일어나는지를 규명하는 것은 암화와 관련된 estrogen의 분자생물학적 작용기전을 이해하는 데 중요한 진전을 가져올 수 있다. 따라서 본 연구의 목적은 유방암세포 내에서 estrogen의 작용이 xenobiotic nuclear receptor에 의해 조절되는지를 규명하기 위하여, 두 종류의 유방암세포인 estrogen receptor가 발현되는 MCF-7 세포와 ER의 발현이 일어나지 않는 MDA-MB-231세포를 배양하여, 에스트로겐에 의해 전사가 촉진되는 보고유전자의 발현이 CAR, SXR, 그리고 PPAR${\gamma}$에 의해서 어떻게 영향을 받는지를 조사하고 그 결과를 간암세포에서의 반응과 비교 분석하였다. 최근에 보고된 연구결과와 일치하게, xenobiotic nuclear receptor가 간세포에서 일어나는 에스트로겐 수용체의 신호전달경로에 영향을 줄 수 있음을 확인하였다. PPAR${\gamma}$를 제외한 핵 수용체 CAR와 SXR은 ER의 전사활성 효과를 현저하게 또는 어느 정도 각각 감소시켰다. Hep G2세포에서와는 달리 유방암세포에서는 조사된 세가지의 xenobiotic 핵 수용체가 ER의 전사활성에 그다지 영향을 미치지 않거나 유방암세포의 종류와 각각의 수용체에 따라서 다소 촉진하는 경향을 나타내었다. MCF-7 세포에서는 CAR와 PPAR${\gamma}$을 제외한 SXR이 ER의 transactivation 효과를 약간 촉진한 반면 MDA-MB-231세포는 SXR을 제외한 CAR와 PPAR${\gamma}$에 의해 ER의 transactivation 효과가 약간 증가되는 경향을 보였다. 이러한 결과는 유방암세포에서는 CAR, SXR, PPAR${\gamma}$과 같은 xenobiotic nuclear receptor에 의한 ER transactivation 효과가 간암세포와는 다르게 나타나며, 유방암의 종류에 따라서 endogenous CAR, SXR, PPAR${\gamma}$수용체가 다르게 발현됨으로써 이들에 대한 반응이 서로 상이한 특징을 나타낼 수 있을 것으로 사료된다. 따라서 estrogen receptor에 의해 매개되는 estrogn의 전사활성조절기전이 표적세포에 따라 다른 경로를 포함 할 수 있음을 시사한다.

• 대한핵의학회:학술대회논문집
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• 대한핵의학회 1975년도 제14차 학술대회
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• pp.84.2-85
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• 1975

• 대한생식의학회:학술대회논문집
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• 대한생식의학회 2007년도 제53차 추계학술대회 초록집
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• pp.39-39
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• 2007

• Asian Pacific Journal of Cancer Prevention
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• 제14권4호
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• pp.2185-2190
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• 2013

Gallbladder carcinoma, the most frequent malignant neoplasm of the biliary tract system, has always been considered to feature late clinical presentation and diagnosis, limited treatment options and an extremely poor prognosis. In recent years, while the incidence of gallbladder cancer has appeared to be on the increase, the available treatment methods have not greatly improved survival of the affected patients. Thus, exploring new therapeutic targets for this devastating disease is an urgent matter at present. Epidemical studies have demonstrated that the incidence of gallbladder carcinoma exhibits a distinct gender bias, affecting females two to three times more than males, pointing to crucial roles of estrogen. It is well known that estrogen acts on target tissues by binding to estrogen receptors (ERs), which are mainly divided into three subtypes, $ER{\alpha}$, $ER{\beta}$ and $ER{\gamma}$. $ER{\alpha}$ and $ER{\beta}$ appear to have overlapping but also unique even opposite biological effects. As important pathogenic mediators, ERs have been considered to relate to several kinds of tumors. In gallbladder carcinoma tissue, ERs have been shown to be positively expressed, and ERs expression levels are associated with differentiation and prognosis of this cancer. Nevertheless, the exact mechanisms of estrogen inducing growth of gallbladder carcinoma remain poorly understood. On the base of the current investigations, we deduce that estrogen participates in promotion of gallbladder carcinoma by influencing the formation of gallstones, stimulating angiogenesis, and promoting abnormal proliferation. Since ERs mediate the carcinogenic actions of estrogen in gallbladder, and therapy targeting ERs may provide new directions for gallbladder carcinoma. Therefore, it should be stressed that ERs are potential therapeutic targets for gallbladder carcinoma.