• BMB Reports
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• v.49 no.9
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• pp.488-496
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• 2016

Estrogens are the key hormones regulating the development and function of reproductive organs in all vertebrates. Recent evidence indicates that estrogens play important roles in the immune system, cancer development, and other critical biological processes related to human well-being. Obviously, the gonads (ovary and testis) are the primary sites of estrogen synthesis, but estrogens synthesized in extra- gonadal sites play an equally important role in controlling biological activities. Understanding non-gonadal sites of estrogen synthesis and function is crucial and will lead to therapeutic interventions targeting estrogen signaling in disease prevention and treatment. Developing a rationale targeting strategy remains challenging because knowledge of extra-gonadal biosynthesis of estrogens, and the mechanism by which estrogen activity is exerted, is very limited. In this review, we will summarize recent discoveries of extra-gonadal sites of estrogen biosynthesis and their local functions and discuss the significance of the most recent novel discovery of intestinal estrogen biosynthesis.

• Toxicological Research
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• v.19 no.4
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• pp.325-330
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• 2003

The effects of estrogen on apoptosis induced by 2,3,7,8-tetrachlorodibenzo-p-doxin (TCDD) were examined in cultured MCF-7 cells. TCDD stimulated apoptosis and inhibited the expression of bcl-2 gene in MCF-7 cells grown in the media supplemented with 10% fetal bovine serum. However, TCDD failed to induce apoptosis if cells were grown in the media deprived of all estrogen-like compounds. Removal of estrogen-like compounds from the growth media also led to the activation of bcl-2 gene expression in cells treated with TCDD. Combined treatment of estrogen with TCDD abrogated the binding of Aryl hydrocarbon Receptor (AhR)-TCDD complex to Dioxin response element (DRE) of bcl-2 gene leading to the inhibition of bcl-2 gene expression as well as stimulation of apoptosis. The present study suggests that the binding of estrogen receptor (ER)-estrogen complex to the estrogen responsive element (E) interferes with the binding of AhR- TCDD complex to the DRE and inhibits the bcl-2 expression.

• Archives of Pharmacal Research
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• v.16 no.4
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• pp.276-282
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• 1993

This study has been undertaken to examine the effect of 3-methylcholanthrene (3MC) on rat uterine growth and to understand the mechanism of action of 3MC in rat uterus. After diethylstilbesterol(DES) or tamoxifen(TAM) or 3MC or DES plus TAM or DES plus 3MC was administered into immature female rats, uterine weight over corn oil-treated uteri. 3MC treatment had no effect on uterine weight but, DES stimulated uterine weight was inhibited by 3MC concomitant tratment. While TAM alone treatment showed slight increase in uterine wieght, inhibited uterine growth simulated by DES when it was adiministrated with DES condirect binding assay with $[^3H]$ estradiol and the relative binding affinities of 3MC and TAM were estimated by competetion assy. Estradiol tumed out to have high affinity for rat uterine estrogen receptor (kd = 0.4 nM). The relative binding affinities of TAM and 3MC were 1% and 4.7% that of DES for rat uterine estrogen receptor, respectively. 3MC was shown to have similar affinity for eat uterine estrogen receptor to that of TAM. Effects of DES 3MC and TAM administration in vivo on rat uterine estrogen recptor level were examined. It was confirmed that the estrogen, DES and antiestrogen, TAM decreased estrogen receptor levels from rat ulterus and also 3MC decreased rat uterine estrogen receptor level when rats were treated with DES, TAM and 3MC in vivo. Data indicates that 3MC acts as an antiestrogen mediated through estrogen receptor system.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.18 no.3
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• pp.515-527
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• 1996

The most serious problem resulting from estrogen deficiency induce osteo porosis. Recently, they make efforts to inquire a relation between hematopoietic organ and bone loss due to estrogen deficiency. Estrogen have an effect on growth and formation of skeletal system, and inhibit bone resorption under the influence of osteoblast and osteoclast, and basically inhibit the increase of hematopoietic progenitor and immune factor connected with bone resorption and prevent the osteoid formation. The purpose of this article was to observe the change of spleen and effect on hematopoietic function following estrogen administration. In this study, female rats of 150g weight was ovariectomized, after 70 days, experimental group was injected estrogen at interval of a week and sacrificed on 1, 2, 3, 4, 6 weeks. Control group was sacrificed after ovariectomy on 11, 12, 13, 14, 16 weeks without estrogen injection, and normal rats were sacrificed for harvest of spleen and femur. Paraffin sections and H&E stain was performed, and observed under light microscope. The obtained results were as follows. 1. From 11 to 12 weeks at bone marrow of control group, hematopoietic cells were decreased in comparison with normal group, and lipid infiltration was seen, and irregular bone remodelling was seen after 13 weeks. From 14 to 16 weeks, there were more decreased hematopoietic cells and lipid degeneration, and lipid degeneration of hematopoietic cells appeared. 2. All the bone marrow of experimental group, the structure of hematopoietic cells with decreased lipid infiltration was recovered from 2 weeks of estrogen adminstration and maintained to 6 weeks. 3. At spleen of control group, borders of white and red pulp was not well demarcated, and size of white pulp was decreased. 4. At spleen of experimental group, borders between white and red pulp have been well demarcated from 3 weeks of estrogen adminstration relatively, and white pulp was increased with distinct border. From above findings, we could regarded that estrogen deficiency due to ovariectomy influenced on hematopoietic cells of bone marrow and spleen, and histologic recovery of hematopoietic cells were observed after 3 weeks of estrogen adminstration even if it was not reach to normal group.

• Asian-Australasian Journal of Animal Sciences
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• v.23 no.8
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• pp.1118-1126
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• 2010

Male reproduction is influenced by a number of intrinsic and extrinsic factors, including environmental endocrine disruptors. Testosterone is a well recognized intrinsic regulator for development and function of the male reproductive tract, and thus male fertility. The testis and semen of many mammalians contain an unusually high concentration of estrogen. Testosterone is converted into estrogen by the enzymatic action of cytochrome P450 aromatase complex (Cyp19a1). Of the male reproductive tract, the efferent ductules (EDs) possess exceptionally elevated levels of estrogen receptors (ERs), ER${\alpha}$ and ER${\beta}$, indicating that estrogen, in addition to testosterone, would have a functional role in regulation of male reproduction. First, this review has focused on description and summary of what is currently known for functions of estrogen in the EDs. The biosynthetic pathway of estrogen occurring in the testis is briefly covered, following by detailed explanation of the morphology and physiology of EDs. In the next section, the sources and targets of estrogen in the male reproductive tract are highlighted, and possible functional roles of estrogen in the EDs are justified from the aspect of physiology, molecular biology, and morphology in adult animal models. Also, this section covers the importance of estrogen and ERs in maintaining normal function and morphology of the EDs during postnatal development. In the last part of this review, the effects of extrinsic factors, especially environmental endocrine-disruptors, on the EDs is summarized. The intent of this review is to emphasize the importance of estrogen for regulation of physiological function of the EDs, and thus male fertility.

• Clinical and Experimental Reproductive Medicine
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• v.30 no.2
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• pp.151-163
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• 2003

연구목적: Estrogen은 포유류의 생리주기와 착상과정에서 중요한 조절인자로 작용한다. 본 연구에서는 난소 절제된 생쥐의 자궁에서 estrogen에 의해 직접 또는 간접적으로 조절되어 발현하는 유전자를 분석하고자 하였다. 연구재료 및 방법: 생후 8주된 생쥐의 양쪽 난소를 절제하고 14일 동안 회복기간이 지난 후, estrogen (300 ng/mouse)을 피하로 주사하였다. Estrogen 주사 후 6, 12시간째 자궁을 적출하여 cDNA microarray와 laser capture microdissection (LCM) 기술을 이용하여 estrogen에 의해 조절되는 유전자의 시공간적인 발현 양상을 조사하였다. 결 과: Estrogen 주사 후 6시간째에는 조사된 전체 유전자 가운데 0.9% (증가 22, 감소 49), 12시간째에는 8.4% (증가 351, 감소 287)에 해당되는 유전자가 두 배 이상 증가 혹은 감소하는 결과를 보였다. 또한 일부 증감된 유전자를 선택한 후 LCM 기술을 이용하여 시공간적인 발현양상을 확인한 결과 자궁내막상피세포에서만 estrogen에 의해 유전자의 발현이 증가되는 일부 유전자를 선별하였다. 결 론: 이상의 결과들을 종합해보면 1) estrogen에 의해 조절되는 유전자의 수나 증감의 정도는 12시간 이후에 더 많고, 크게 조절되며, 2) 유전자의 조절부위가 자궁의 특이적인 세포층에서 시공간적으로 조절됨을 의미한다. 이러한 유전자의 정보는 생리주기 또는 착상과정의 분자생물학적 기작을 이해하는 데 도움이 될 것이다.

• Journal of Nutrition and Health
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• v.38 no.1
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• pp.30-39
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• 2005

The effects of different concentrations of estrogen supplementation to mature female rats or estrogen supplementation to ovariectomized rats on cyclooxygenase-2 (COX-2) expression, PGE$_2$ production and mapkinases expression were investigated in experimentally induced atherogenic rats with feeding a high fat. high cholesterol diet. In the first experiment using 48-week old mature rats, the supplementation of three different levels of estrogen was compared to the basal diet. The high concentration of estrogen supplementation induced the marked up-regulation of COX-2 protein and the increase in plasma PGE$_2$ production and this seems to be followed by the up-regulation of p38 among mapkinases. The regulation of bax showed in a reverse trend of COX-2 in heart tissues of mature female rats. In the second ex-perimental system, female Sprague-Dawley rats were bilaterally ovariectomized; sham-operated animals were used as controls. Three weeks later, the animals were supplied with basal diet to sham-operated control group and ovariectomized control group, and estrogen supplemented diet to ovariectomized group for an eight-week experimental period. In a group supplemented with a medium dose of estrogen, COX-2 expression was up-regulated. This up-regulation was accompanied by the elevated expression of pERK1/2. Bax was increased in estrogen-fed animals indicating bax might be involved in estrogen feeding state in ovariectomized rats. Further investigations on the relationship between COX-2 and biological activities such as vasodilation by estrogen are required in in vivo system of female rats at the various physiological states.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.4
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• pp.2371-2375
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• 2013

Breast cancer is one of the most common malignancies in women around the world. Among the various hormonal types of breast cancer, those that are estrogen receptor (ER) positive account for the majority. Among the estrogen related receptors, estrogen related receptor ${\alpha}$ is known to have a potential role in breast cancer and is one of the therapeutic target. Hence, prediction of novel ligands interact with estrogen related receptor alpha is therapeutically important. The present study, aims at prediction and analysis of ligands from the KEGG COMPOUND database (containing 10,739 entries) able to interact against estrogen receptor alpha using a similarity search and molecular docking approach.

• Biomedical Science Letters
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• v.10 no.4
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• pp.479-483
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• 2004

The aim of this study was carried to the induction of follistatin-like 1 (FSTL1) in rat myometrium tissue by exogenous estrogen. PCR was performed by using estrogen treatment after ovariectomy of myometrium mRNA and only ovariectomy of myometrium mRNA and on ovariectomy of myometrium mRNA in rat normal uterus tissue. The PCR products were visualized on agarose gel (1.2％) electrophoresis. FSTL1 mRNA expression level was significantly higher (**P<0.001 or *P<0.05) in estrogen treatment after ovariectomy than in only ovariectomy, and was significantly higher (**P<0.001) in no ovariectomy than in estrogen with treatment after ovariectomy. In conclusion, Although the mechanisms of FSTL1 gene were uncertain, It also might be inducted by exogenous estrogen. And also it is thought to be related to the estorgen mechanism.

• Biomedical Science Letters
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• v.24 no.3
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• pp.143-149
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• 2018

Excessive exposure to estrogens is the most important risk factor for the development of hormone-sensitive cancers, especially breast cancer. Estrogen stimulates the expression of genes and proteins involved in cell proliferation by binding to estrogen receptor (ER). Another possible mechanism of ER-independent carcinogenicity of estrogens is based on the hydroxylation of estradiol resulting in the formation of catechol estrogens. Catechol estrogen 4-hydroxyestradiol ($4-OHE_2$) is further oxidized to catechol estrogen-3,4-quinones, the major carcinogenic metabolites of estrogens. Evidence increasingly supports the critical role of $4-OHE_2$ in hormonal carcinogenesis via DNA adduct formation or production of reactive oxygen species, which finally contribute to the transformation of normal mammary epithelial cells and the enhanced growth of breast cancer cells. It is also reported that the level of $4-OHE_2$ or its quinones is highly up-regulated in urine or tissues of breast cancer patients. Thus, we highlight the oncogenic roles of $4-OHE_2$ in catechol estrogen-induced breast carcinogenesis.