• Archives of Pharmacal Research
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• 제20권6호
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• pp.566-571
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• 1997

To gain further insight into how estrogens modulate cell function, the effects of estrogen on cell proliferation were studied inhuman breast cancer cells. We examined the effects of estrogen on the proliferation of three human breast cancer cell lines that differed in their estrogen receptor contents. Ten nM estradiol markedly stimulated the proliferation of MCF-7 human breast cancer cells that contained high levels of estrogen receptor $1.15{\pm}0.03 pmole/mg protein)$(over that of control. In T47D cells that contained low levels of estrogen receptor $0.23{\pm}0.05 pmole/mg protein)$, Ten nM estrogen slightly stimulated the proliferation over that of control. MDA-MB-231 cells, that contained no detectable levels of estrogen receptors, had their growth unaffected by estrogen. These results showed their sensitivity to growth stimulation by estrogen correlated well with their estrogen receptor content. Also we examined the effect of estrogen on cellular progesterone receptor level as well as plasminogen activator activity in MCF-7 cells. Ten nM estradiol showed maximal stimulation of progesterone receptor level as well as plasminogen activator activity in MCF-7 cells. It is not clear whether these stimulations of progesterone receptor and plasminogen activator activity by estrogen are related to the estrogen stimulation of cell proliferation of MCF-7 cells. Studies with estrogen in human breast cancer cells in culture indicate that sensitivity to growth stimulation by estrogen correlates well with estrogen receptor contents.

• 대한수의학회지
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• 제37권2호
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• pp.281-289
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• 1997

The study was designed to investigate the effects of progesterone and estrogen on the uterus of rats by immunohistochemical methods using Proliferating Cell Nuclear Antigen (PCNA) antibody. Eighteen female rats(Wistar), weighing initially about 300g, were ovariectomized. These rats were divided into four groups, progesterone-treated group, estrogen-treated group, estrogen+progesterone-treated group, and control group, progesterone-treated group was injected with 1mg of progesterone per rat per day for 2 days and estrogen-treated group with $20{\mu}g$ of $17{\beta}-estradiol$ for 3 days and estrogen+progesterone-treated group with $17{\beta}-estrdiol$ for 3 days and then with progesterone for 2 days as above. In gross findings, the uteri were markedly hypertrophied by estrogen treatment but were not affect in size by progesterone treatment. Immunohistochemical investigation was performed on the cell types with higher appearance of PCNA positive reaction cells in four groups. The groups with higher appearance of the stromal cells were ordered as estrogen-treated group, progesterone-treated group, estrogen+progesterone-treated group, and control group. The muscle cells were ordered as progesterone-treated group, estrogen-treated group, estrogen+progesterone-treated group, and control group. Positive reaction cells of the stromal cells were total 4.6 times higher than those of muscle cells. Therefore, the affect of the hypertrophy on the uterus by estrogen was larger than those of progesterone and affect on the uterus by stromal cells were larger than those of muscle cells. The group with more PCNA positive reaction cells of luminal epithelial cells were ordered as control group, progesterone-treated group, estrogen+progesterone-treated group, and estrogen-treated group, and glandular epithelial cells were ordered as estrogen+progesterone-treated group, progesterone-treated group, control group, and estrogen-treated group. It was suggested that estrogen and progesterone did not affect on the proliferating cells of luminal epithelial cells and affection of progesterone on the development of glandular epithelial cell was larger than that of estrogen.

• Toxicological Research
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• 제35권3호
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• pp.209-214
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• 2019

Cancer is the leading cause of mortality worldwide. In cancer progression, sex hormones and their receptors are thought to be major factors. Many studies have reported the effects of estrogen and estrogen receptors (ERs) in cancer development and progression. Among them, G protein-coupled estrogen receptor (GPER), a G protein-coupled receptor, has been identified as an estrogen membrane receptor unrelated to nuclear ER. The mechanism of GPER, including its biological action, function, and role, has been studied in various cancer types. In this review, we discuss the relation between GPER and estrogen or estrogen agonists/antagonists and cancer progression.

• Archives of Pharmacal Research
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• 제20권6호
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• pp.579-585
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• 1997

To gain further insight into the mechanism of action of antiestrogens, we examined the interaction of antiestrogen with the estrogen receptor system and with estrogen- noncompetable antiestrogen binding sites. In addition to binding directly to the estrogen receptor, antiestrogens can be found associated with binding sites that are distinct from the estrogen receptor. In contrast to the restriction of estrogen receptors to estrogen target cells, such as those of uterus and mammary glands, antiestrogen binding sites are present in equal amounts in estrogen receptor-positive and -negative human breast cancer cell lines, such as MCF-7, T47D, and MDA-MB-231 that differ markedly in their sensitivity to antiestrogens. In order to gain greater insight into the role of these antiestrogen binding sites in the action of antiestrogens, we have examined the biopotency of different antiestrogens for the antiestrogen binding sites and that is CI628 > tamoxifen > trans-hydroxy tamoxifen > CI628M > H1285 > LY117018. This order of affinities does not parallel the affinity of these compounds for the estrogen receptor nor the potency of these compounds as antiestrogens. Indeed, compounds with high affinity for the estrogen receptor and greatest antiestrogenic potency have low affinities for these antiestrogen binding sites. Antiestrogenic potency correlates best with estrogen receptor affinity and not with affinity for antiestrogen binding sites. In summary, our findings suggested that interaction with the estrogen receptor is most likely the mechanism through which antiestrogens evoke their growth inhibitory effects.

• 한국식품영양과학회지
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• 제25권6호
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• pp.1006-1015
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• 1996

본 연구는 폐경 후 여성에게 식이 칼슘염 형태, 에스트로겐 및 에스트로겐/칼슘 혼합요법이 칼슘, 인 및 질소 대사에 미치는 영향을 알아보고자 난소절제쥐를 이용한 총 9군으로 분류하여 6주간 사육한 후, 섭취량과 배설량을 측정하였고, 이로부터 흡수율과 평형상태를 구하였다. 난소를 절제한 군과 난소를 절제하지 않은 군에서의 칼슘 섭취량은 비슷하였으나 소변으로의 칼슘 배설이 난소를 절제한 군에서 유의하게 높았다. 난소절제 후 estrogen투여 및 estrogen/칼슘 혼합 투여군에서의 소변으로의 칼슘 배설량은 낮은 경향을 보였다. 대변으로의 칼슘 배설량은 난소를 절제한 군이 난소를 절제하지 않은군에 비해 유의하게 높았다(p<0.001). 난소절제 후 estrogen을 투여한 결과 대변으로의 칼슘 배설량은 감소하였다. 고칼슘을 투여한 군들 모두에서 대변으로의 칼슘 배설량이 현저히 높았다. 칼슘의 외견적 흡수율은 난소를 절제한 군에 비해 난소를 절제하지 않은 군이 유의하게 높았다. 난소절제 후 고칼슘을 투여한 군들에 비해 난소절제 후 estrogen을 투여한 군이 난소절제 군에 비해 외견적 흡수율이 증가하였다. 칼슘 평형은 난소절제 후 고칼슘을 투여한 군들에서 난소를 절제한 군 보다 유의하게 높은 양의 칼슘 평형상태를 보였다. 난소를 절제한 군과 난소를 절제하지 않은 군에서의 소변으로의 인 배설은 난소를 절제한 군이 다소 증가하였다. 난소절제 후에 고칼슘 투여, estrogen 투여, estrogen/칼슘 혼합 투여군에서의 소변으로의 인 배설이 유의하게 감소하였다(p<0.01). 난소를 절제한 군과 난소를 절제하지 않은 군에서의 대변으로 인 배설량은 난소를 절제한 군이 많았으며 난소절제 후 estrogen 투여군에서는 대변으로의 인 배설량이 다른 군 보다 적었다. 난소절제 후 고칼슘 투여군에서는 대변으로의 인 배설이 다소 증가한 경향이었다. 인의 평형상태도 난소를 절제하지 않은 군에서 유의하게 높았다. 난소절제 후 고칼슘 투여, estrogen 투여, estrogen/칼슘 혼합 투여 및 estrogen점진적 감소와 고칼슘 투여에 의한 효과로는 인의 평형이 다소 증가하였으나 난소를 절제하지 않은 군에 비해서는 평형이 현저히 낮았다. 난소를 절제한 군과 난소를 절제하지 않은 군에서 소변으로의 질소 배설량은 난소를 절제한 군에서 유의 하게 높았으며 난소절제 후 estrogen, estrogen/칼슘 혼합 투여, estrogen 점진적 감소와 칼슘 점진적 증가군에서 각각 배설량이 감소하였다. 대변으로의 질소 배설량은 난소를 절제한 군에서 유의하게 높았다. Estrogen투여에 의해 대변으로의 질소 배설이 감소하였다. 고칼슘 투여군들은 대변으로의 질소배설이 높았다. 이상의 성적으로 보아 난소절제로 인해 칼슘, 인, 질소 평형이 난소를 절제하지 않은 군에 비하여 낮아졌다. 난소를 절제한 군에 비해 난소절제 후 고칼슘 투여, estrogen/칼슘 혼합, estrogen 점진적 감소와 칼슘 점진적 증가군에서 칼슘 평형을 증가 시켰다. 그러나 인과 질소 평형에는 큰 영향을 미치지 않았다.

• BMB Reports
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• 제44권7호
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• pp.423-434
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• 2011

A female hormone, estrogen, is linked to breast cancer incidence. Estrogens undergo phase I and II metabolism by which they are biotransformed into genotoxic catechol estrogen metabolites and conjugate metabolites are produced for excretion or accumulation. The molecular mechanisms underlying estrogen-mediated mammary carcinogenesis remain unclear. Cell proliferation through activation of estrogen receptor (ER) by its agonist ligands and is clearly considered as one of carcinogenic mechanisms. Recent studies have proposed that reactive oxygen species generated from estrogen or estrogen metabolites are attributed to genotoxic effects and signal transduction through influencing redox sensitive transcription factors resulting in cell transformation, cell cycle, migration, and invasion of the breast cancer. Conjuguation metabolic pathway is thought to protect cells from genotoxic and cytotoxic effects by catechol estrogen metabolites. However, methoxylated catechol estrogens have been shown to induce ER-mediated signaling pathways, implying that conjugation is not a simply detoxification pathway. Dual action of catechol estrogen metabolites in mammary carcinogenesis as the ER-signaling molecules and chemical carcinogen will be discussed in this review.

• BMB Reports
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• 제51권5호
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• pp.225-229
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• 2018

In humans, hormonal regulation is crucial for the preparation of uterine environment leading to either successful implantation or menstrual cycle. Estrogen is a pivotal female steroid hormone that regulates the uterine dynamics along with progesterone in the estrous and menstrual cycles in humans. Estrogen signals act via nuclear estrogen receptor or membrane-bound receptor. The membrane-bound estrogen receptor plays a crucial role in the rapid response of estrogen in the uterine epithelium. Recently, RASD1 has received attention as a novel signal transducer of estrogen in various systems including female reproductive organs. In this review, we discuss the regulation of estrogen and RASD1 signaling in the uterus and also provide insights into RAS as a novel signaling molecule in repeated implantation failure.

• Clinical and Experimental Reproductive Medicine
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• 제29권4호
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• pp.279-285
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• 2002

Objective : To evaluate the difference between estrogen only therapy and estrogen-androgen combination therapy in surgical menopause patients. Materials and Method: Surgical menopause patients received 0.625 mg conjugated equine estrogens or 0.625 mg conjugated equine estrogens plus 1.25 mg methyltestosterone for 2 years. Bone mineral density, menopausal symptoms, lipoprotein profiles were measured. Results: Both groups showed increased bone mineral density. In the combination group, total cholestero l, high density lipoprotein cholesterol and triglycerides decreased. In the estrogen only group, low density lipoprotein cholesterol decreased but high density lipoprotein cholesterol increased significantly. In both groups, menopausal symptoms were much improved. Side effects were easily tolerated in both groups. Conclusions: Estrogen-androgen combination therapy had comparable benefits compared with estrogen only therapy.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 2003년도 Annual Meeting of KSAP : International Symposium on Pharmaceutical and Biomedical Sciences on Obesity
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• pp.114-114
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• 2003

Ginseng is a medicinal herb widely used in Asian countries, and its pharmacological effects has been demonstrated in various systems such as cardiovascular, central nervous, and endocrine systems. Its effects are mainly attributed to the ginsenosides. We hypothesize that a component of Panax ginseng, ginsenoside-Rbl, acts by binding to estrogen receptor. We have investigated the estrogenic activity of ginsenoside-Rbl in a transient transfection system using estrogen receptors ${\alpha}$ or ${\beta}$ with estrogen -responsive luciferase plasmids in COS monkey kidney cells. Ginsenoside-Rbl activated both estrogen receptors ${\alpha}$ and ${\beta}$ in a dose-dependent manner (0.5 -100 M ). Activation was inhibited by the specific estrogen receptor antagonist ICI 182,780, indicating that the estrogenic effect of ginsenoside-Rbl is estrogen receptor dependent. Next, we evaluated the ability of ginsenoside-Rbl to induce estrogen-responsive progesterone receptor gene by semi-quantitative RT-PCR assays. MCF-7 cells treated with l7${\beta}$-estradiol or ginsenoside- Rb1 exhibited an increased expression of progesterone receptor mRNA. However, ginsenoside-Rbl failed to displace the specific binding of ［3H］17${\beta}$-estradiol to estrogen receptor in MCF-7 cells as examined by whole cell ligand binding assays, suggesting that there is no direct interaction of ginsenoside-Rbl with estrogen receptor. Our results indicate that estrogen-like activity of ginsenoside-Rbl is independent of direct estrogen receptor association.

• 대한약리학회지
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• 제26권2호
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• pp.167-176
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• 1990

비스테로이드성 항에스트로젠제는 표적기관에서 estrogen 수용체와 상경적으로 결합하므로써 estrogen의 작용을 억제하는 것으로 알려져 있다. 비스테로이드성 항에스트로젠제는 대체로 triphenylethylene계로서 tamoxifen, clomiphene, LYl17018등이 있으며 표적기관에서 estrogen의 작용을 억제하기 때문에 estrogen과 관련된 질환을 치료하는데 이용되어 오고 있다. 본 연구에서는 생후 21-23일된 미성숙 흰쥐를 재료로 항에스트로젠제중 tamoxifen과 LY117018이 자궁세포 성장에 어떠한 영향을 미치며 어떠한 기전으로 estrogen의 작용을 길항하는지를 규명하고자, 항에스트로젠제가 estrogen작용의 중요 지포에 미치는 영향을 비교 관찰하여 다음과 같은 결과를 얻었다. Tamoxifen과 LY117018은 자궁세포에서 estrogen의 영향이 없는 경우에는 estrogen agonist로, estrogen작용하에서는 estrogen antagonist로서 작용하였다. Estrogen 작용의 여러 가지 지표에 대해 tamoxifen이 LY117018보다 agonistic effect는 더 컸으나, antagonistic effect는 LY117018이 더 큰 것으로 나타났다. Estrogen 수용체에 대한 결합능은 LY117018이 estradiol보다는 약간 낮았으나 용량에 비례하여 estrogen 수용체와 결합하였다. 그러나 tamoxifen은 estrogen 수용체에 대한 결합이 아주 낮았다. Estrogen 수용체에 대한 binding affinity는 estradiol(100%), LY117018(77%), tamoxifen(6.3%) 순으로 나타났다. 항에스트로젠제의 생체내 투여는 estrogen 존재 유무에 따라 estrogen 수용체 농도에 agonist 또는 antagonist로 작용하였다. 항에스트로젠제의 단독투여는 progesterone 수용체 생성을 증가시키나, estrogen에 의하여 유도된 progesterone 수용체 생성을 억제하였다. 이상의 결과로 보아, tamoxifen과 LY117018은 estrogen유무에 따라 흰쥐 자궁세포에서 estrogen antagonist로서 뿐만 아니라 agonist로서도 작용함을 알 수 있다. 그러나 estrogen수용체와의 결합능력이 아주 낮은 tamoxifen은, 용량에 비례하여 estrogen수용체에 결합하므로써 작용하는 LY117018과는 다른 기전으로 작용하는 것으로 생각된다.