• Title/Summary/Keyword: estrogen receptor-$\alpha$

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Improvement of the Biosensor for Detection of Endocrine Disruptors by Combination of Human Estrogen Receptorα and Co-Activator (Human Estrogen Receptor α와 Co-activator로 구성된 바이오센서를 이용한 내분비계장애물질의 검출)

  • Lee, Haeng-Seog
    • Journal of Korean Society of Water and Wastewater
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    • v.20 no.6
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    • pp.893-904
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    • 2006
  • To improve sensitivity of biosensor as yeast two-hybrid detection system for estrogenic activity of suspected chemicals, we tested effects of several combinations of the bait and fish components in the two-hybrid system on Saccharomyces cerevisiae inducted a chromosome-integrated lacZ reporter gene that was under the control of CYC1 promoter and the upstream Gal4p-binding element $UAS_{GAL}$. The bait components that were fused with the Gal4p DNA binding domain are full-length human estrogen receptor ${\alpha}$ and its ligand-binding domain. The fish components that were fused with the Gal4p transcriptional activation domain were nuclear receptor-binding domains of co-activators SRC1 and TIF2. We found that the combination of the full-length human estrogen receptor ${\alpha}$ with the nuclear receptor-binding domain of co-activator SRC1 was most effective for the estrogen-dependent induction of reporter activity among the two-hybrid systems so far reported. The relative strength of transcriptional activation by representative natural and xenobiotic chemicals was well correlated with their estrogenic potency that had been reported with other assay systems.

Molecular Cloning of Estrogen Receptor $\alpha$ in the Masu Salmon, Oncorhynchus masou

  • Sohn, Young Chang
    • Journal of Aquaculture
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    • v.17 no.1
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    • pp.62-68
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    • 2004
  • A cDNA encoding the masu salmon, Oncorhynchus masou, estrogen receptor $\alpha$ (msER$\alpha$) was cloned from the pituitary gland by polymerase chain reaction (PCR). This cDNA contains an open reading frame encoding 513 amino acid residues, and the calculated molecular weight of this protein is about 56,430 Dalton. The amino acid sequences of the DNA binding and ligand binding domains of msER$\alpha$ showed high homology to those of other fish species (84-100%). Reverse transcription PCR analysis showed that the mRNA level of msER$\alpha$ in the pituitary was slightly higher in estradiol-17$\beta$(E2) injected masu salmon than that of control fish. To test the biological activity of msER$\alpha$, the cDNA was ligated to a mammalian expression vector and transfected into a gonadotrope-derived cell line, L$\beta$T2, with a reporter plasmid including estrogen responsive element. Expression of the reporter protein, luciferase, was E2 and msER$\alpha$-dependent. The masu salmon ER$\alpha$ is structurally conserved among teleost species and functions as a transcriptional activator in the pituitary cells.

The Distributions of Three Genetic Polymorphisms in the Estrogen $Receptor-\alpha$ Gene in Korean Essential Hypertensives (한국인 본태성 고혈압군에서 에스트로젠 수용체-$\alpha$(유전자에 존재하는 다형성의 분포에 관한 연구)

  • Kim Ji Young;Kang Byung Yong;Lee Kang Oh
    • Environmental Analysis Health and Toxicology
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    • v.20 no.3 s.50
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    • pp.249-258
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    • 2005
  • Blood pressure, obesity and bone mineral density are multifactorial traits influenced by genetic factor. The purpose of this study was to clarify the association between three genetic polymorphisms in the estrogen receptor-$\alpha$ (ER -$\alpha$) gene and essential hypertension in korean population. One hundred and seventy-one people including 90 normotensives and 81 essential hypertentives were recruited. Among genetic polymorphisms studied, the Xba I RFLP in the intron 1 of this gene polymorphism was significantly associated with essential hypertension in women, suggesting the sexual dimorphism in genetic effect (P (<) 0.05). Further studied suggest that a larger sample size of this study are needed.

Estrogen Receptor Alpha Agonist Propyl Pyrazole Triol Causes Alterations of the Morphology and Function of the Mouse Male Reproductive System

  • Lee, Eun-Jung;Cho, Hyun-Wook
    • Animal cells and systems
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    • v.13 no.2
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    • pp.205-212
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    • 2009
  • Known as a female hormone, estrogen, performs important functions, and the activities of the hormone are mediated via the estrogen receptor. The principal objective of the present study was to assess the effects of a estrogen receptor agonist in male reproductive organs. In this study, the estrogen receptor alpha agonist, PPT, was injected subcutaneously into adult male mice. The effects of PPT on the murine reproductive system were histologically assessed at 3,5, and 8 weeks after treatment. In the treatment group, reductions were observed in the weight of the body, testis and epididymis. Microscopic examination revealed a reduction in seminiferous tubular diameter in the testis, and epithelial cell height in the epididymis during the experiment. 8 weeks after treatment, spermatogenesis was not detected, nor was the lumen of the seminiferous tubules. In the fertility test, 1 week after PPT injection, the fertilizing ability of males was decreased, and on the 2nd and 3rd weeks, complete infertility was observed. In conclusion, the injection of high concentrations of PPT into adult males induced physiological changes, including infertility, and also induced morphological changes, including a reduction in the height of epithelial cells within the reproductive system.

Assessment of Adipocyte Differentiation and Maturation-related Gene Expression in the Epididymal Fat of Estrogen Receptor α Knockout (ERαKO) Mouse during Postnatal Development Period

  • Cheon, Yong-Pil;Ko, CheMyong;Lee, Ki-Ho
    • Development and Reproduction
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    • v.24 no.4
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    • pp.287-296
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    • 2020
  • The absence of functional estrogen receptor α (Esr1) results in an overgrowth of the epididymal fat, as observed in estrogen receptor α knockout (ERαKO) mouse. The present research was aimed to evaluate expression of various molecules associated with adipocyte differentiation and maturation in the epididymal fat of ERαKO mouse at several postnatal ages by using quantitative real-time polymerase chain reaction. The highest transcript levels of all molecules were detected at 12 months of postnatal age, except leptin which the mRNA level was increased at 5 months of age and was unchanged until 12 months of age. The expression levels of CCAAT enhancer binding protein (Cebp) alpha, androgen receptor, and lipoprotein lipase were decreased at 5 months of age but increased at about 8 months of age. The mRNA levels of Cebp gamma and sterol regulatory element binding transcription factor 1 remained steady until 8 months of age. Continuous increases of transcript levels during postnatal period were found in Cebp beta, estrogen receptor (ER) beta, fatty acid binding protein 4, and delta like non-canonical Notch ligand 1. The increases of peroxisome proliferator-activated receptor gamma and adiponectin mRNA levels were detected as early as 8 months of age. The levels of fatty acid synthase and resistin transcript at 5 and 8 months of age were lower than that at 2 months of age. These findings show the aberrant expression patterns of genes related to adipocyte differentiation and maturation in the postnatal epididymal fat pad by the disruption of ER alpha function.

Estrogen Receptor-α Mediates the Effects of Estradiol on Telomerase Activity in Human Mesenchymal Stem Cells

  • Cha, Young;Kwon, Su Jin;Seol, Wongi;Park, Kyung-Soon
    • Molecules and Cells
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    • v.26 no.5
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    • pp.454-458
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    • 2008
  • Sex steroid hormone receptors play a central role in modulating telomerase activity, especially in cancer cells. However, information on the regulation of steroid hormone receptors and their distinct functions on telomerase activity within the mesenchymal stem cell are largely unavailable due to low telomerase activity in the cell. In this study, the effects of estrogen ($E_2$) treatment and function of estrogen receptor alpha ($ER{\alpha}$) and estrogen receptor beta ($ER{\beta}$) on telomerase activity were investigated in human mesenchymal stem cells (hMSCs). Telomerase activity and mRNA expression of the catalytic subunit of telomerase (hTERT) were upregulated by treatment of the cells with $E_2$. The protein concentration of $ER{\alpha}$ was also increased by $E_2$ treatment, and enhancement of $ER{\alpha}$ accumulation in the nucleus was clearly detected with immunocytochemistry. When $ER{\alpha}$ expression was reduced by siRNA transfection into hMSCs, the effect of $E_2$ on the induction of hTERT expression and telomerase activity was diminished. In contrast, the transient overexpression of $ER{\alpha}$ increased the effect of $E_2$ on the expression of hTERT mRNA. These findings indicate that the activation of hTERT expression and telomerase activity by $E_2$ in hMSCs depends on $ER{\alpha}$, but not on $ER{\beta}$.

Endocrinic Effects of Toxaphene and Chlordane in Human Hepatoma Cell (HepG2 Cell) Transfected with Estrogen Receptor and Luciferase Reporter Gene (에스트로겐 수용체 및 Luciferase 리포터 유전자 도입 사람 간 종양세포(HepG2 Cell)에서 Toxaphene과 Chlordane의 내분비 독성)

  • Kim Kyeong-Bae;Jung Ji-Won;Yang Se-Ran;Kang Kyung-Sun;Lee Yong-Soon
    • Toxicological Research
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    • v.20 no.3
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    • pp.205-211
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    • 2004
  • Concern that some chemicals in our environment may affect human health by disrupt-ing normal endocrine function has prompted a research on interactions of environmental contaminants with steroid hormone receptor. Toxaphene and chlordane are among the 12 persistent organic pollutants identified by the United Nations Environment Programme as requiring urgent attention. We compared the estrogenic activity of two organochlorine pesticides, toxaphene and chlordane, at estrogen receptor a (ER$\alpha$) and estrogen receptor $\beta$ (ER$\beta$). Human hepatoma cells (HepG2) were transiently transfected with rat ER$\alpha$ or ER$\beta$ plus an estrogen-responsive complement C3-luciferase (C3-Luc) reporter gene. After transfection, cells were treated with various concentrations of toxaphene and chlordane to investigate agonism or antagonism of these chemicals. Both toxaphene and chlordane were potent agonists in HepG2 cells for ER$\alpha$. In contrast, these chemicals had a minimal agonist activity with ER$\beta$ and almost abolished 17$\beta$-estradiol-induced ER$\beta$-mediated activity. Therefore, toxaphene and chlordane behaved as an ER$\alpha$ agonist and an ER$\beta$ antagonist with estrogen-responsive reporter plasmid C3-Luc, and exposure to these organochlorine pesticides could have a crictical effect on normal endocrine function.

Mechanisms of Inhibitory Ah Receptor-Estrogen Receptor Crosstalk in Breast Cancer Cells

  • Safe, Stephen H.
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2003.10b
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    • pp.23-23
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    • 2003
  • 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and other aryl hydrocarbon (AhR) ligands suppress 17${\beta}$-estradiol (E)-induced responses in the rodent uterus and mammary tumors and in human breast cancer cells. Treatment of ZR-75, T47D and MCF-7 human breast cancer cells with TCDD induces proteasome-dependent degradation of endogenous estrogen receptor ${\alpha}$ (ER${\alpha}$).(omitted)

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Estrogen Receptor α Regulates Dlx3-Mediated Osteoblast Differentiation

  • Lee, Sung Ho;Oh, Kyo-Nyeo;Han, Younho;Choi, You Hee;Lee, Kwang-Youl
    • Molecules and Cells
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    • v.39 no.2
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    • pp.156-162
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    • 2016
  • Estrogen receptor ${\alpha}$ (ER-${\alpha}$), which is involved in bone metabolism and breast cancer, has been shown to have transcriptional targets. Dlx3 is essential for the skeletal development and plays an important role in osteoblast differentiation. Various osteogenic stimulators and transcription factors can induce the protein expression of Dlx3. However, the regulatory function of ER-${\alpha}$ in the Dlx3 mediated osteogenic process remains unknown. Therefore, we investigated the regulation of Dlx3 and found that ER-${\alpha}$ is a positive regulator of Dlx3 transcription in BMP2-induced osteoblast differentiation. We also found that ER-${\alpha}$ interacts with Dlx3 and increases its transcriptional activity and DNA binding affinity. Furthermore, we demonstrated that the regulation of Dlx3 activity by ER-${\alpha}$ is independent of the ligand (estradiol) binding domain. These results indicate that Dlx3 is a novel target of ER-${\alpha}$, and that ER-${\alpha}$ regulates the osteoblast differentiation through modulation of Dlx3 expression and/or interaction with Dlx3.

PKA-Mediated Stabilization of FoxH1 Negatively Regulates ERα Activity

  • Yum, Jinah;Jeong, Hyung Min;Kim, Seulki;Seo, Jin Won;Han, Younho;Lee, Kwang-Youl;Yeo, Chang-Yeol
    • Molecules and Cells
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    • v.28 no.1
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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.