• 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.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1999.04a
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• pp.5-8
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• 1999

여성의 breast cancer의 1/3 의 경우가 hormone-dependent에 의한 것이다. 따라서 그 치료의 접근 방법으로써 estrogen receptor에 작용하거나, receptor-mediated gene trenscription을 저해하는 antiestrogen을 사용하는 것이 있다. Estrogen은 microsomal cytochrome P-450 enzyme complex system에 의해 androgen으로부터 생합성되는 hormone이며, estrogen product는 steroid product의 biosynthetic sequence의 마지막 단계에서 생산되고, aromatase는 이에 관여하는 enzyme으로써, aromatase를 선택적으로 저해하는 경우에 다른 steroid의 생산에 영향을 미치지 않고 estrogen 생산을 감소 시킬 수 있다. 이러한 관점에서, aromatase를 선택적으로 저해하는 것은 hormone-dependent breast cancer를 완화시킬 수 있는 가능성을 가진 cancer chernopreventive agents의 새로운 방법이라 할 수 있다.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.1
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• pp.89-94
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• 2002

Effect of Gamisamul-tang(GS) on body weight, uterine weight, splenial weight, serum and estrogen receptor-α (ER-α) in kidney were investigated in ovariectomized(OVX) rats. Female Sprague -Dawley rats with a body weight of 220 g were undergone ovariectomy or sham operation. The ovariectomy caused significant decrease in serum levels of HDL-cholesterol and in uterine weight compared to those of sham-operated animals. while caused significant increase in serum levels of total cholesterol, LDL-cholesterol, triglyceride, body weight and in splenial weight. In contrast, administration of OVX rats with the GS significantly elevated serum levels of HDL-cholesterol and uterine weight, but significantly depressed serum levels of total cholesterol, LDL-cholesterol, triglyceride, body weight and in splenial weight. ER-α localized in the kidney vessel endothelial cells and its expression was increased by ovariectomy and decreased by administration of OVX rats with the GS. Our results suggest that a possible protective effect of as against hyperlipidemia in postmenopausal cardiovascular disease and as increase the estrogen-estrogen receptor romp/ex in the kidney vessel endothelial cells.

• Journal of Ginseng Research
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• v.43 no.4
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• pp.527-538
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• 2019

Background: Ginsenoside Rg1 was shown to exert ligand-independent activation of estrogen receptor (ER) via mitogen-activated protein kinase-mediated pathway. Our study aimed to delineate the mechanisms by which Rg1 activates the rapid ER signaling pathways. Methods: ER-positive human breast cancer MCF-7 cells and ER-negative human embryonic kidney HEK293 cells were treated with Rg1 ($10^{-12}M$, $10^{-8}M$), $17{\beta}$-estradiol ($10^{-8}M$), or vehicle. Immunoprecipitation was conducted to investigate the interactions between signaling protein and ER in MCF-7 cells. To determine the roles of these signaling proteins in the actions of Rg1, small interfering RNA or their inhibitors were applied. Results: Rg1 rapidly induced $ER{\alpha}$ translocation to plasma membrane via caveolin-1 and the formation of signaling complex involving linker protein (Shc), insulin-like growth factor-I receptor, modulator of nongenomic activity of ER (MNAR), $ER{\alpha}$, and cellular nonreceptor tyrosine kinase (c-Src) in MCF-7 cells. The induction of extracellular signal-regulated protein kinase and mitogen-activated protein kinase kinase (MEK) phosphorylation in MCF-7 cells by Rg1 was suppressed by cotreatment with small interfering RNA against these signaling proteins. The stimulatory effects of Rg1 on MEK phosphorylation in these cells were suppressed by both PP2 (Src kinase inhibitor) and AG1478 [epidermal growth factor receptor (EGFR) inhibitor]. In addition, Rg1-induced estrogenic activities, EGFR and MEK phosphorylation in MCF-7 cells were abolished by cotreatment with G15 (G protein-coupled estrogen receptor-1 antagonist). The increase in intracellular cyclic AMP accumulation, but not Ca mobilization, in MCF-7 cells by Rg1 could be abolished by G15. Conclusion: Ginsenoside Rg1 exerted estrogenic actions by rapidly inducing the formation of ER containing signalosome in MCF-7 cells. Additionally, Rg1 could activate EGFR and c-Src ER-independently and exert estrogenic effects via rapid activation of membrane-associated ER and G protein-coupled estrogen receptor.

• Reproductive and Developmental Biology
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• v.38 no.1
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• pp.35-40
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• 2014

Beta-catenin (CTNNB1, catenin (cadherin-associated protein), beta 1) is involved in various biological processes, including embryogenesis, tumorigenesis, angiogenesis and progression of metastasis. CTNNB1, as a multifunctional and oncogenic protein, has important roles in adhesion between Sertoli cells through an N-cadherin-dependent manner and in various cancer types through its over-activation. In addition, CTNNB1 can interact with estrogen/estrogen receptor alpha complex, which regulates the transcription of WNT (wingless-type MMTV integration site family)/CTNNB1 target genes. Recently, we investigated the functional roles and expression pattern of CTNNB1 during the morphological changes of embryonic gonads of chickens and the estrogen-dependent regulation of CTNNB1 in oviduct development and potential functions as a biomarker of CTNNB1 in human epithelial ovarian cancer using the chicken as a biological research model. Therefore, in this review, we provide a new insight of potential role of CTNNB1 in the development of the female reproductive tract during early embryogenesis and ovarian carcinogenesis of laying hen models.

• Proceedings of the Korean Society of Developmental Biology Conference
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• 2003.10a
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• pp.69-69
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• 2003

Neuroprotective strategies have been appeared to be effective in a variety of stroke models. One of the major focuses has been related to the activities of estrogen. $17\beta$-estradiol valerate(EV) has been reported to exert neuroprotective effects when administered before an ischemic insult. The purpose of this study was to determine whether EV can protect against brain injury via estrogen receptor. Chronic and acute pretreatment can reduce the ischemic damage of focal cerebral ischemia in OVX rat, indicating that EV may be a new therapeutic class of drugs to prevent neuronal damage associated with cerebral ischemia. RNAs were extracted from the hippocampus of ovariectomized female rat with or without EV. Differential gene expression profiles were revealed(Bone morphogenetic protein type 1A receptor, Protein disulphide isomerase, cytochrome bc-1 complex core P, thiol-specific antioxidant protein). RT-PCR and in situ hybridization were used to validate the relative expression pattern obtained by the cDNA array. This Study was supported by the Korea Science and Engineering Foundation(KOSEF) through the Biohealth Products Research Center(BPRC), Inje University, Korea

• Journal of Life Science
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• v.28 no.2
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• pp.265-273
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• 2018

Estrogen (E2) is involved in the development and progression of breast cancer and is mediated by estrogen receptor (ER). ER plays important roles in cellular proliferation, migration, invasion and causing drug resistance through diverse cross-talks with epidermal growth factor receptor (EGFR) and insulin-like growth factor-1 receptor (IGF-1R) signaling pathways in breast cancer cells. Breast cancer is caused mainly by break-down of homeostasis of endocrine signaling pathways especially by the uncontrolled expression and increased activities of E2/IGF-1/EGF, ER/G-protein estrogen receptor (GPER)/IGF-1R/EGFR and their intracellular signaling mediators. These changes influence the complex cross-talk between E2 and growth factors' signaling, eventually resulting in the progression of cancer and resistance against endocrine regulators. Thus, elucidation of the molecular mechanisms in stepwise of the cross-talk between E2 and growth factors will contribute to the customized treatment according to the diverse types of breast cancer. In particular, as strategies for the treatment of breast cancer with diverse genotypes and phenotypes, there can be use of aromatase inhibitors and blockers of E2 action for the ER+ hormone-dependent breast cancer cells and use of IGF-1R/EGFR activity blockers for suppression of cancer cell proliferation from the cross-talk between E2 and growth factors. Furthermore, changes in the expression of the ECM molecules regulated by the cross-talk between ER and EGFR/IGF-1R can be used for the targeted therapeutics against the migration of breast cancer cells. Therefore, it is required for the cross-talk among the signaling pathways of ER, GPER, IGF-1R and EGFR concerning cancer progression to be elucidated in more detail at the molecular level.

• BMB Reports
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• v.47 no.11
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• pp.643-648
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• 2014

Stanniocalcin (STC), a glycoprotein hormone originally discovered in fish, has been implicated in calcium and phosphate homeostasis. While fishes and mammals possess two STC homologs (STC1 and STC2), the physiological roles of STC2 are largely unknown compared with those of STC1. In this study, we identified Ran-binding protein M (RanBPM) as a novel binding partner of STC2 using yeast two-hybrid screening. The interaction between STC2 and RanBPM was confirmed in mammalian cells by immunoprecipitation. STC2 enhanced the RanBPM-mediated transactivation of liganded androgen receptor (AR), but not thyroid receptor ${\beta}$, glucocorticoid receptor, or estrogen receptor ${\beta}$. We also found that AR interacted with RanBPM in both the absence and presence of testosterone (T). Furthermore, we discovered that STC2 recruits RanBPM/AR complex in T-dependent manner. Taken together, our findings suggest that STC2 is a novel RanBPM-interacting protein that promotes AR transactivation.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.6
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• pp.903-910
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• 2016

In this study, the expression level of estrogen receptor in an ovariectomized rat model was effectively enhanced by MS-10, Cirsium japonicum and Thymus vulgaris extract complex, in a reversible manner. MS-10 plays a positive role in enhancing estrogen activity at low concentrations, leading to improved women's health. In order to determine whether or not MS-10 improves menopausal symptoms clinically, a randomized, double-blinded, and placebo-controlled clinical study was carried out on 62 middle-aged women treated with 500 mg of MS-10 or placebo daily for 12 weeks. Clinical menopausal symptoms were evaluated by Kupperman's index (KI) detecting various menopausal symptoms, including hot flushes, parenthesis, insomnia, nervousness, melancholia, dizziness, fatigue, rheumatic pain, palpitations, formication, and headaches. Total KI score decreased significantly by about 18% upon ingestion of MS-10. Colpoxerosis, a main symptom of menopause, was significantly reduced by about 21% upon ingestion of MS-10 in contrast to placebo. In addition, reduction of insulin-like growth factor-1 with age was improved by over 10% upon ingestion of MS-10, whereas there were no significant difference with placebo. No side effects appeared after treatment with MS-10. Thus, MS-10 can be suggested as a plausible natural substance for improving women's health.

• Development and Reproduction
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• v.13 no.3
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• pp.133-143
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• 2009

Pivotal roles of steroid hormones in uterine endometrial function are well established from the mouse models carrying the null mutation of their receptors. Literally androgen belongs to male but interestingly it also detected in female. The fluctuations of androgen levels are observed during reproductive cycle and pregnancy, and the functional androgen receptor is expressed in reproductive organs including uterus. Using high throughput methodology, the downstream genes of androgen have been isolated and revealed correlations between other steroid hormones. In androgen-deficient mice, uterine responses to exogenous gonadotropins are impaired and the number of pups per litter is reduced dramatically. As expected androgen has important role in decidual differentiation through AR. It regulates specific gene network during those cellular responses. Recently we examined the effects of steroid hormonal complex containing high level of androgen. Interestingly, on the contrary to the androgen-alone administration, the hormonal complex did not disturb the decidual reaction and the pubs did not show any morphological abnormality. It is suspected that the complexity of communication between other steroid hormone and their receptors are the reasons. In summary, androgen exists in female blood and it suggests the importance of androgen in female reproduction. However, the complex interactions with other hormones are not fully understood compared with estrogen and progesterone. The further studies to evaluate the possible role of androgen are needed and important to provide the in vivo rational for the prevention of associated pregnancy complications and help human's health.