• Title/Summary/Keyword: ER-${\alpha}$

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Effect of Prepubertal Exposure to Di(2-ethylhexyl)phthalate on the Maturation of Rat Seminal Vesicles and Prostate Glands (사춘기 전 수컷 흰쥐의 저정낭과 전립선의 성숙에 미치는 Di(2-ethylhexyl) phthalate(DEHP)의 영향)

  • Heo, Hyun-Jin;Lee, Won-Yong;Yoon, Yong-Dal;Choi, Donchan;Lee, Sung-Ho
    • Development and Reproduction
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    • v.12 no.3
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    • pp.251-259
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    • 2008
  • The plasticizer di(2-ethylhexyl)phthalate(DEHP) is one of the most well known endocrine disrupting chemicals (EDCs) because of its strong anti-androgenic effects on the reproductive and developmental process in male rodents and human. The present study was performed to examine whether prepubertal exposure to DEHP can make any alteration during the maturation of accessory sex organs in male rats. As a result, there was no significant change in body weights, serum T levels and tissue weights except of seminal vesicle and ventral prostate in DEHP-treated animals compared to vehicle-treated ones. The seminal vesicle weights in high-dose group (200 mg/kg) were significantly lower than those from the control group (p<0.05), and ventral prostate weights were significantly lower than those from the control group (p<0.05) in both low-dose (20 mg/kg) and high-dose group. Histological studies revealed that the seminal vesicles from DEHP-treated groups showed reduced areas of mucosal folds. Pseudostratified columnar epithelia were observed in the ventral prostates of DEHP-treated samples while cuboidal epithelia were found in the control group. The transcriptional activities of ER-$\alpha$ in seminal vesicle from high-dose group (p<0.05) were significantly higher than those from the control group, and ER-$\beta$ expression was significantly decreased in low-dose group (p<0.05) compared to the control. In ventral prostate, ER-$\beta$ mRNA levels from low-dose group (p<0.05) were significantly lower than those from the control group, and significantly increased in high-dose group (p<0.01). AR expressions, however, were not significantly different in all experimental groups of both seminal vesicle and ventral prostate. In conclusion, the present study demonstrated that (i) adverse effect (s) of DEHP on sexual maturation during prepubertal period could be limited, (ii) seminal vesicle and prostate gland were sensitive targets to DEHP in prepubertal rats and (iii) the deleterious effects of DEHP might be mediated through ER-associated mechanism.

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Sex-Hormone Replacement Effect of Silkworm Pupa and Mixture with Herbs (미성숙 흰쥐에서 누에 번데기 및 한약재 혼합물의 여성호르몬 대체효과)

  • Yang Ji-Won;Choi Eun-Mi;Kwon Mu-Gil;Koo Sung-Ja
    • Korean journal of food and cookery science
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    • v.21 no.6 s.90
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    • pp.769-775
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    • 2005
  • In this study we isolate substances to serve as dietary resources in order to replace the female hormone. Silkworm (Bombyx mori) is one of the most attractive hosts for large-scale production of eukaryotic proteins which have been proven safe as a dietary resource. We report on the estrogenicity of a mixture of silkworm pupa and herbs (Ginseng,Ulkeum, and Hasuo) using the immature rat uterotrophic assay in vivo. Silkworm pupa aqueousextract (KW) and silkworm oil extract (KO) induced effects on the immature rat uterotrophic assay. KO showed neither positive uterotrophic response nor inhibition on E2 induced effect, while KW and MK (mixture of KW and herbs) showed both of the effects. It is concluded that ethanol extracts from silkworm might be a good, therapeutic, natural product for hormone-deficient diseases.

Alteration of Gene Expressions in Human Endometrial Stromal Cells by Exogeneous FSH Treatments (난포자극호르몬이 인간의 자궁 기질세포의 유전자 발현 양상에 미치는 영향)

  • Choi, Hye-Won;Jun, Jin-Hyun;Lee, Hyoung-Song;Hong, In-Sun;Kang, Kyung-Sun;Koong, Mi-Kyoung
    • Clinical and Experimental Reproductive Medicine
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    • v.31 no.4
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    • pp.217-223
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    • 2004
  • Objective: To evaluate the effects of recombinant FSH (rFSH) and urinary FSH (uFSH) on the gene expressions of human endometrial stromal cells in vitro. Methods: Endometrial tissue was obtained from a pre-menopausal women undergoing hysterectomy. Primary endometrial stromal cells were isolated and in vitro cultured with FBS-free DMEM/F-12 containing 0, 10, 100, and 1, 000 mIU/ml of rFSH and uFSH for 48 hours, respectively. Total RNA was extracted from the cultured cells and subjected to real time RT-PCR for the quantitative analysis of progesterone receptor (PR), estrogen receptor $\alpha/\beta$ (ER-$\alpha/\beta$), cyclooxygenase 2 (Cox-2), leukemia inhibitory factor (LIF), homeobox A10-1 and -2 (HoxA10-1/-2). Results: Both hormone treatments slightly increased (< 3 folds) the expressions of PR, ER-$\beta$ and HoxA10-1/-2 gene. However, ER-$\alpha$ expression was increased up to five folds by treatments of both FSH for 48 hours. The LIF expression by the 10 mIU/ml of uFSH for 12 hours was significantly higher than that of rFSH (p<0.01). After 24 hours treatment of two kinds of hormones, the expression patterns of LIF were similar. The 100 and 1, 000 mIU/ml of rFSH induced significantly higher amount of Cox-2 expression than those of uFSH, respectively (p<0.05). Conclusion: This study represents no adversely effect of exogeneous gonadotropins, rFSH and uFSH, on the expression of implantation related genes. We suggest that rFSH is applicable for the assisted reproductive technology without any concern on the endometrial receptivity.

17β-estradiol mediated effects on pluripotency transcription factors and differentiation capacity in mesenchymal stem cells derived porcine from newborns as steroid hormones non-functional donors

  • Lee, Won-Jae;Park, Ji-Sung;Lee, HyeonJeong;Lee, Seung-Chan;Lee, Jeong-Hyun;Ock, Sun-A;Rho, Gyu-Jin;Lee, Sung-Lim
    • Journal of Embryo Transfer
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    • v.32 no.3
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    • pp.209-220
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    • 2017
  • The estrogen-mediated effect of mesenchymal stem cells (MSCs) is a highly critical factor for the clinical application of MSCs. However, the present study is conducted on MSCs derived from adult donors, which have different physiological status with steroid hormonal changes. Therefore, we explores the important role of $17{\beta}$-estradiol (E2) in MSCs derived from female and male newborn piglets (NF- and NM-pBMSCs), which are non-sexually matured donors with steroid hormones. The results revealed that in vitro treatment of MSCs with E2 improved cell proliferation, but the rates varied according to the gender of the newborn donors. Following in vitro treatment of newborn MSCs with E2, mRNA levels of Oct3/4 and Sox2 increased in both genders of MSCs and they may be correlated with both estrogen receptor ${\alpha}$ ($ER{\alpha}$) and $ER{\beta}$ in NF-pBMSCs, but NM-pBMSCs were only correlated with $ER{\alpha}$. Moreover, E2-treated NF-pBMSCs decreased in ${\beta}$-galactosidase activity but no influence on NM-pBMSCs. In E2-mediated differentiation capacity, E2 induced an increase in the osteogenic and chondrogenic abilities of both pBMSCs, but adipogenic ability may increased only in NF-pBMSCs. These results demonstrate that E2 could affect both genders of newborn donor-derived MSCs, but the regulatory role of E2 varies depending on gender-dependent characteristics even though the original newborn donors had not been affected by functional steroid hormones.

Peel strength of denture liner to PMMA and polyamide: laser versus air-abrasion

  • Korkmaz, Fatih Mehmet;Bagis, Bora;Ozcan, Mutlu;Durkan, Rukiye;Turgut, Sedanur;Ates, Sabit Melih
    • The Journal of Advanced Prosthodontics
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    • v.5 no.3
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    • pp.287-295
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    • 2013
  • PURPOSE. This study investigated the effect of laser parameters and air-abrasion on the peel strength of silicon-based soft denture liner to different denture resins. MATERIALS AND METHODS. Specimens (N=180) were prepared out of three different denture base resins (Rodex, cross-linked denture base acrylic resin; Paladent, heat-cured acrylic resin; Deflex, Polyamide resin) ($75mm{\times}25mm{\times}3mm$). A silicon-based soft denture liner (Molloplast B) was applied to the denture resins after the following conditioning methods: a) Air-abrasion ($50{\mu}m$), b) Er,Cr:YSGG laser (Waterlase MD Turbo, Biolase Technology) at 2 W-20 Hz, c) Er,Cr:YSGG laser at 2 W-30 Hz, d) Er,Cr:YSGG laser at 3 W-20 Hz, e) Er,Cr:YSGG laser at 3 W-30 Hz. Non-conditioned group acted as the control group. Peel test was performed in a universal testing machine. Failure modes were evaluated visually. Data were analyzed using two-way ANOVA and Tukey's test (${\alpha}$=.05). RESULTS. Denture liner tested showed increased peel strength after laser treatment with different parameters ($3.9{\pm}0.4-5.58{\pm}0.6$ MPa) compared to the control ($3.64{\pm}0.5-4.58{\pm}0.5$ MPa) and air-abraded groups ($3.1{\pm}0.6-4.46{\pm}0.3$ MPa), but the results were not statistically significant except for Paladent, with the pretreatment of Er,Cr:YSGG laser at 3 W-20 Hz. Polyamide resin after air-abrasion showed significantly lower peel strength than those of other groups ($3.1{\pm}0.6$ MPa). CONCLUSION. Heat-cured acrylic resin, PMMA, may benefit from Er,Cr:YSGG laser treatment at 3 W-20 Hz irradiation. Air-abrasion of polyamide resins should be avoided not to impair their peel bond strengths to silicon-based soft denture liners.

Effect of Estrogen on Ovariectomy-Induced Obesity in Rats (난소절제술로 유도된 흰쥐 비만에서 에스트로젠의 작용)

  • Chu, Sang-Hui;Lee, Mi-Kyung;Kowalski, Jill;Beck, Jenny;Schwertz, Dorie
    • Journal of Korean Biological Nursing Science
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    • v.10 no.1
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    • pp.80-87
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    • 2008
  • Purpose: Hypoestrogenism caused by ovariectomy, disease, or menopause is associated with increased obesity in women. Altered fat distribution and weight gain are consequences of menopausal hypoestrogenism, but the mechanisms responsible are not completely known. This study examined the effect of estrogen on obesity in ovariectomized rats. Method: The groups of female rats were 4 weeks post ovariectomy (OVX) or, 4 weeks post-sham operation (SHAM), and 2 weeks post ovariectomy followed by 2 weeks replacement with estradiol benzoate (ER-$16{\mu}g$/kg, subq, qd). Serum ghrelin level was measured by radioimmunoassay (RIA). The expression of adrenergic receptors in adipose tissue was measured by Western blotting assay. Result: OVX significantly increased body weight, serum cholesterol. Two weeks estrogen replacement reduced body weight accompanied by the increment of serum ghrelin and the reduction of the receptor ratio of adrenergic ${\alpha}_{2A}/{\beta}_1$, and ${\alpha}_{2A}/{\beta}_3$. Conclusion: We provide evidence that estrogen reduces obesity through the altered receptor ratio of adrenergic ${\alpha}_{2A}/{\beta}_1$, and ${\alpha}_{2A}/{\beta}_3$ in adipose tissue in ovariectomized rats.

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Kisspeptin-10 Enhanced Egg Production in Quails Associated with the Increase of Triglyceride Synthesis in Liver

  • Wu, J.;Fu, W.;Huang, Y.;Ni, Y.;Zhao, R.
    • Asian-Australasian Journal of Animal Sciences
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    • v.26 no.8
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    • pp.1080-1088
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    • 2013
  • Our previous results showed that kisspeptin-10 (Kp-10) injections via intraperitoneal (i.p.) once daily for three weeks notably promoted the egg laying rate in quails. In order to investigate the mechanism behind the effects of Kp-10 on enhancing the egg laying rate in birds, this study focused on the alternations of lipids synthesis in liver after Kp-10 injections. 75 female quails (22 d of age) were allocated to three groups randomly, and subjected to 0 (control, Con), 10 nmol (low dosage, L) and 100 nmol (high dosage, H) Kp-10 injections via i.p. once daily for three weeks, respectively. At d 52, quails were sacrificed and sampled for further analyses. Serum $E_2$ concentration was increased by Kp-10 injections, and reached statistical significance in H group. Serum triglyceride (TG) concentrations were increased by 46.7% in L group and 36.8% in H group, respectively, but did not reach statistical significance, and TG contents in liver were significantly elevated by Kp-10 injections in a dose-dependent manner. Serum total cholesterol (Tch) concentrations significantly decreased in H group, while in H group the hepatic Tch content was markedly increased. The level of non-esterified fatty acid (NEFA), apolipoprotein A1 and B (apoA1 and apoB) were not altered by Kp-10 injections. The genes expression of sterol regulatory element binding protein-1 (SREBP-1), fatty acid synthetase (FAS), apolipoprotein VLDL-II (apoVLDL-II), cholesterol $7{\alpha}$-hydroxylase (CYP7A1) and vitellogenin II (VTG-II) were significantly up-regulated by high but not low dosage of Kp-10 injection compared to the control group. However, the expression of SREBP-2, acetyl-CoA carboxylase ($ACC_{\alpha}$), malic enzyme (ME), stearoyl-CoA (${\Delta}9$) desaturase 1 (SCD1), apolipoprotein A1 (apoA1), fatty acid binding protein 2 (FABP2), 3-hydroxyl-3-methyl glutaryl-coenzyme A reductases (HMGCR), estrogen receptor ${\alpha}$, ${\beta}$($ER{\alpha}$ and ${\beta}$) mRNA were not affected by Kp-10 treatment. In line with hepatic mRNA abundance, hepatic SREBP1 protein content was significantly higher in H group. Although the mRNA expression was not altered, the content of $ER{\alpha}$ protein in liver was also significantly increased in H group. However, SREBP-2 protein content in liver was not changed by Kp-10 treatment. In conclusion, exogenous Kp-10 consecutive injections during juvenile stage significantly advanced the tempo of egg laying in quails, which was associated with the significant elevation in hepatic lipids synthesis and transport.

Use of Oral Antidiabetic Drugs (Metformin and Pioglitazone) in Diabetic Patients with Breast Cancer: How Does It Effect on Serum Hif-1 Alpha and 8Ohdg Levels?

  • Ece, Harman;Cigdem, Erten;Yuksel, Kucukzeybek;Ahmet, Dirican;Hakan, Er;Oktay, Tarhan Mustafa
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.10
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    • pp.5143-5148
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    • 2012
  • Objective: The aim was to investigate indicators related to DNA damage and cancer pathogenesis in Type II diabetes cases with breast cancer. It was planned to evaluate the relationship between these markers with oral antidiabetic drugs. Research Design and Methods: Fourty patients and 10 healthy individuals were included in the study. HIF-$1{\alpha}$ and 8-OHdG are examined in blood samples taken from these individuals with an ELISA Kit. Statistical analysis of data was performed with 95% confidence using Windows package program SPSS 15.0. Results: HIF-$1{\alpha}$ parameters were found to be meaningfully higher in the patient group than the controls in both pretreatment and posttreatment periods (p<0.05). No significant differences in terms of 8-OHdG between patients and controls. However, posttreatment serum HIF-$1{\alpha}$ ve 8-OHdG levels was found lower than pretreatment levels in patients receiving metformin, but not with pioglitazone. Conversely, serum 8-OHdG levels decreased significantly in these patients. When patients were evaluated according to the treatment groups (pioglitazone vs. metfformin) no significant differences in terms of serum HIF-$1{\alpha}$ and 8-OHdG levels between treatment groups. Conclusions: HIF-$1{\alpha}$ levels decreased significantly in the patient group receiving metformin. However, there was no significant difference in terms of HIF-$1{\alpha}$ levels in the patients receiving pioglitazone.

Salubrinal-Mediated Upregulation of eIF2α Phosphorylation Increases Doxorubicin Sensitivity in MCF-7/ADR Cells

  • Jeon, Yong-Joon;Kim, Jin Hyun;Shin, Jong-Il;Jeong, Mini;Cho, Jaewook;Lee, Kyungho
    • Molecules and Cells
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    • v.39 no.2
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    • pp.129-135
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    • 2016
  • Eukaryotic translation initiation factor 2 alpha ($eIF2{\alpha}$), which is a component of the eukaryotic translation initiation complex, functions in cell death and survival under various stress conditions. In this study, we investigated the roles of $eIF2{\alpha}$ phosphorylation in cell death using the breast cancer cell lines MCF-7 and MCF-7/ADR. MCF-7/ADR cells are MCF-7-driven cells that have acquired resistance to doxorubicin (ADR). Treatment of doxorubicin reduced the viability and induced apoptosis in both cell lines, although susceptibility to the drug was very different. Treatment with doxorubicin induced phosphorylation of $eIF2{\alpha}$ in MCF-7 cells but not in MCF-7/ADR cells. Basal expression levels of Growth Arrest and DNA Damage 34 (GADD34), a regulator of $eIF2{\alpha}$, were higher in MCF-7/ADR cells compared to MCF-7 cells. Indeed, treatment with salubrinal, an inhibitor of GADD34, resulted in the upregulation of $eIF2{\alpha}$ phosphorylation and enhanced doxorubicin-mediated apoptosis in MCF-7/ADR cells. However, MCF-7 cells did not show such synergic effects. These results suggest that dephosphorylation of $eIF2{\alpha}$ by GADD34 plays an important role in doxorubicin resistance in MCF-7/ADR cells.

Human Papillomavirus Type 16/18 Oncoproteins: Potential Therapeutic Targets in Non-smoking Associated Lung Cancer

  • Zhang, Er-Ying;Tang, Xu-Dong
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.11
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    • pp.5363-5369
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    • 2012
  • High-risk human papillomavirus (HPV) especially HPV-16 and HPV-18 types are speculated to be important risk factors in non-smoking associated lung cancer in Asia. Increasing evidence has demonstrated that HPV oncoproteins may contribute to lung tumorigenesis and cell transformation. Importantly, HPV 16/18 E6 and E7 oncoproteins can mediate expression of multiple target genes and proteins, such as p53/pRb, VEGF, HIF-$1{\alpha}$, cIAP-2, and hTERT, and contribute to cell proliferation, angiogenesis and cell immortalization through different signaling pathways in lung cancer. This article provides an overview of experiment data on HPV-associated lung cancer, describes the main targets on which HPV E6/E7 oncoproteins act, and further discusses the potential signaling pathways in which HPV E6/E7 oncoproteins are involved. In addition, we also raise questions regarding existing problems with the study of HPV-associated lung cancer.