• BMB Reports
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• 제48권7호
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• pp.367-368
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• 2015

It has long been thought that glucocorticoid receptor (GR) functions as a DNA-binding transcription factor in response to its ligand (a glucocorticoid) and thus regulates various cellular and physiological processes. It is also known that GR can bind not only to DNA but also to mRNA; this observation points to the possible role of GR in mRNA metabolism. Recent data revealed a molecular mechanism by which binding of GR to target mRNA elicits rapid mRNA degradation. GR binds to specific RNA sequences regardless of the presence of a ligand. In the presence of a ligand, however, the mRNA-associated GR can recruit PNRC2 and UPF1, both of which are specific factors involved in nonsense-mediated mRNA decay (NMD). PNRC2 then recruits the decapping complex, consequently promoting mRNA degradation. This mode of mRNA decay is termed "GR-mediated mRNA decay" (GMD). Further research demonstrated that GMD plays a critical role in chemotaxis of immune cells by targeting CCL2 mRNA. All these observations provide molecular insights into a previously unappreciated function of GR in posttranscriptional regulation of gene expression. [BMB Reports 2015; 48(7): 367-368]

• 한국어류학회지
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• 제22권1호
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• pp.17-24
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• 2010

본 연구에서는 감성돔의 염분과 수온 변화에 따른 스트레스 반응을 알아보기 위하여 glucocorticoid receptor (GR) mRNA 발현을 조사하였다. 감성돔 신장으로부터 전장의 GR cDNA를 클로닝하였고, 염분과 수온이 변화하는 동안 아가미, 신장 및 장에서 GR mRNA 발현 변화를 quantitative real-time PCR (QPCR)을 이용하여 조사하였다. 염분 변화시, 아가미, 신장 및 장에서 GR mRNA 발현은 0 psu에서 가장 높게 나타났으며, 혈장 cortisol과 glucose 농도도 증가한 반면, triiodothyronine ($T_3$) 농도는 감소하였다. 수온 변화시, 아가미, 신장 및 장에서 GR mRNA 발현은 $30^{\circ}C$에서 가장 높게 관찰되었다. 혈장 cortisol, glucose 및 $T_3$ 농도 또한 고수온 ($30^{\circ}C$)에서 증가하였다. GR mRNA 발현의 증가는 염분과 수온 변화와 같은 환경 요인에 대한 좋은 스트레스 지표로 여겨진다.

• BMB Reports
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• 제42권7호
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• pp.421-426
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• 2009

Glucocorticoids regulate multiple physiological processes such as metabolic homeostasis and immune response. Mouse Pon2 (mPon2) acts as an antioxidant to reduce cellular oxidative stress in cells. In this present study, we investigated the transcriptional regulation of mPon2 by glucocorticoids. In the presence of glucocorticoid analogue dexamethasone, the expression of mPon2 mRNA in cells was increased, whereas the expression was inhibited by a transcription inhibitor actinomycin D. Glucocorticoid receptors bound to the putative glucocorticoid response elements located between -593 bp and -575 bp of the mPon2 promoter. Transcriptional activity was completely blocked when the putative element was mutated. Taken together, these results suggest that the expression of the mPon2 gene is directly regulated by glucocorticoid-glucocorticoid receptor complexes.

• 한국어류학회지
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• 제20권3호
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• pp.149-155
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• 2008

The effects of noise stress response on hematological parameters (hemoglobin, hematocrit and MCHC) and plasma parameters (cortisol, glucose and albumin) in Korean rockfish (Sebastes schlegeli), a very important commercial marine fish in Korea, were investigated. These parameters were analyzed on fish exposed to an explosion of noise. There were no significant differences or trends in hematological parameters (hematocrit; control $29.7{\pm}4.8%$, experiment 32.0 35.5%; hemoglobin; control $6.5{\pm}0.7g/dL$, experiment 6.2 7.8 g/dL; MCHC; control $19.6{\pm}0.6g/dL$, experiment 19.9~22.2 g/dL). However, plasma cortisol and glucose exhibited significant differences from start to finish and displayed the following patterns (cortisol; control $180.7{\pm}35.4ng/mL$, experiment 247.0 444.5 ng/mL; glucose; control $32.5{\pm}6.3mg/dL$, experiment 50.5 109.0 mg/dL). In addition, the glucocorticoid receptor (GR) mRNA expression and basal levels of various tissues (eye, gills, liver, intestine, skin and gonads) were investigated for the first time in this marine fish. When the Korean rockfish was exposed to explosive noise stress, the GR mRNA was expressed more in the gonads than in other tissues tested and was elevated significantly from two and four times in the liver and gills, respectively, after noise exposure.

• 한국수산과학회지
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• 제48권3호
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• pp.346-353
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• 2015

Glucocorticoids (GCs) are steroid hormones regulated through responses to stress to maintain diverse metabolic and homeostatic functions. GCs act on the glucocorticoid receptor (GR), a member of the nuclear receptor family. This study identified and characterized the GR gene from the big-belly seahorse Hippocampus abdominalis designating it HaGR. The open reading frame of the HaGR cDNA was 2,346 bp in length, encoding a 782-amino-acid polypeptide with a theoretical isoelectric point of 6.26 and predicted molecular mass of 86.8 kDa. Nuclear receptors share a common structural organization, comprising an N-terminal transactivation domain, DNA-binding domain, and C-terminal ligand-binding domain. The tissue-specific mRNA expression profile of HaGR was analyzed in healthy seahorses using a qPCR technique. HaGR mRNA was expressed ubiquitously in all of the tissues examined, with the highest expression levels in kidney, intestine, stomach, and gill tissues. The mRNA expression in response to immune challenge with lipopolysaccharide (LPS), polyinosinic:polycytidylic acid (poly I:C), Edwardsiella tarda, and Streptococcus iniae revealed that it is inducible in response to pathogen infection. These results suggest that HaGR is involved in the immune response of the big-belly seahorse.

• 한국수정란이식학회지
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• 제17권3호
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• pp.171-177
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• 2002

Glucocorticoid는 비유기 동물의 유선세포 pro-lactin receptor(PRL-R) 발현을 증가시키며, 전반적인 유선세포의 유합성 작용을 활성시킴으로 유합성 능력을 증진시킨다. 유선세포 PRL-R 발현량 증가는 유생산량 향상과 밀접한 관계를 갖는다. 본 실험은 비유중기의 재래산양의 유합성 능력을 향상시키고자, 0.05. 0.1과 0.2 g hydrocortisone을 5ml의 생리식염수에 현탁하여, 정맥투여하고 유선세포 PRL-R와 $\alpha$-유단백 질 mRNAs 발현 량을 조사하였다. 대조구로는 5$m\ell$의 생리식염수를 정맥투여 하였다. 24시간 후 유선조직을 채취하여 $\alpha$-유단백질과 PRL-R mRNA 발현량을 competitive PCR(polymerase chain reaction)로 발현량을 조사하였다. Hydrocortisone 처리 24시간 후 재래산양 유선세포의 PRL-R mRNA 발현량은 대조구의 PRL-R mRNA 발현량과 유의한 차이가 없었다. $\alpha$-유단백질 mRNA 발현은 대조구에 비하여 0.05g hydrocortisone투여구는 37%, 0.1g hydrocortisone 투여구는 630%, 0.2g hydrocortisone 투여구는 386% 증가하였다. Hydrocortison 처리에 의한 유선세포 PRL-R mRNA 발현에 변화가 없었으나 $\alpha$-유단백질 mRNA 발현 증가는 세포 내 기능성 단백질 발현과 세포 외부로 분비되는 단백질의 시간에 따른 발현양상의 차이인 것으로 사려된다. 본 연구에서 비유중기 재래산양에 hydrocortisone 투여는 $\alpha$-유단백질 mRNA 발현을 증가시키는 것으로 나타났다.

• Journal of Ginseng Research
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• 제41권4호
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• pp.477-486
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• 2017

Background: Our previous studies have demonstrated that ginsenoside-Rg1 can promote angiogenesis in vitro and in vivo through activation of the glucocorticoid receptor (GR). Furthermore, microRNA (miRNA) expression profiling has shown that Rg1 can modulate the expression of a subset of miRNAs to induce angiogenesis. Moreover, Rb1 was shown to be antiangiogenic through activation of a different pathway. These studies highlight the important functions of miRNAs on ginseng-regulated physiological processes. The aim of this study was to determine the angiogenic properties of Korean Red Ginseng extract (KGE). Methods and Results: Combining in vitro and in vivo data, KGE at $500{\mu}g/mL$ was found to induce angiogenesis. According to the miRNA sequencing, 484 differentially expressed miRNAs were found to be affected by KGE. Among them, angiogenic-related miRNAs; miR-15b, -23a, -214, and -377 were suppressed by KGE. Meanwhile, their corresponding angiogenic proteins were stimulated, including vascular endothelial growth factor, vascular endothelial growth factor receptor-2, endothelial nitric oxide synthase, and MET transmembrane tyrosine kinase. The miRNAs-regulated signaling pathways of KGE were then found by Cignal 45-Pathway Reporter Array, proving that KGE could activate GR. Conclusion: KGE was found capable of inducing angiogenesis both in vivo and in vitro models through activating GR. This study provides a valuable insight into the angiogenic mechanisms depicted by KGE in relation to specific miRNAs.

• The Korean Journal of Physiology and Pharmacology
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• 제15권3호
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• pp.163-169
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• 2011

Corticosterone is known to modulate GABAergic synaptic transmission in the hypothalamic paraventricular nucleus. However, the underlying receptor mechanisms are largely unknown. In the anterior hypothalamic area (AHA), the sympathoinhibitory center that project GABAergic neurons onto the PVN, we examined the expression of glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) of GABAergic neurons using intact GAD65-eGFP transgenic mice, and the effects of corticosterone on the burst firing using adrenalectomized transgenic mice. GR or MR immunoreactivity was detected from the subpopulations of GABAergic neurons in the AHA. The AHA GABAergic neurons expressed mRNA of GR (42%), MR (38%) or both (8%). In addition, in brain slices incubated with corticosterone together with RU486 (MR-dominant group), the proportion of neurons showing a burst firing pattern was significantly higher than those in the slices incubated with vehicle, corticosterone, or corticosterone with spironolactone (GR-dominant group; 64 vs. 11~14%, p<0.01 by $x^2$-test). Taken together, the results show that the corticosteroid receptors are expressed on the GABAergic neurons in the AHA, and can mediate the corticosteroid-induced plasticity in the firing pattern of these neurons. This study newly provides the experimental evidence for the direct glucocorticoid modulation of GABAergic neurons in the AHA in the vicinity of the PVN.

• Animal cells and systems
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• 제1권1호
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• pp.115-121
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• 1997

To precisely analyze the role of ovarian steroids in the regulation of laminin chain gene expression in mouse uterine tissues, the ovariectomized mouse model was used. Ovariectomized mice received a single injection of steroid hormones and total RNA was isolated from whole uterine tissues. Messenger RNA levels of each laminin chain (A, 81, and 82) were determined by competitive RT-peR procedures. Estradiol decreased mRNA levels of laminin 81 chain about two-fold, and 82 chain rather moderately. Estradiol-induced inhibition of laminin 81 and 82 chain mRNA levels were completely blocked by pretreatment with estrogen receptor antagonist tamoxifen. Estriol, a short acting estrogen which cannot induce hyperplastic responses of rodent uterine tissues, also showed an inhibitory effect on 81 and 82 chain mRNA levels, while estrone, an inactive estrogen, failed to influence either 8 chain mRNA levels. Effects of steroids on A chain mRNA level were quite different from those on 8 chains. Laminin A chain mRNA level was slightly increased by estradiol treatment, but negatively affected by progesterone. Progesterone treatment greatly increased both 8 chain mRNA levels, but slightly decreased A chain mRNA level compared to the control. The effect of progesterone on laminin chain-specific mRNA levels was further increased by co-injection of estradiol in a time-dependent manner. Progesterone-induced 81 and 82 chain mRNA transcription was inhibited by RU486, a synthetic anti-progesterone /anti-glucocorticoid. The present study demonstrates for the first time that steroids are able to regulate laminin gene expression in mouse uterine tissues, indicating that steroid-regulated laminin gene expression is involved in uterine growth and probably differentiation.

• Archives of Pharmacal Research
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• 제26권1호
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• pp.53-57
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• 2003

We have found that ginsenoside Rc and Re induce c-fos in MCF-7 human breast carcinoma cells at both the mRNA and protein levels. However, neither ginsenoside activated the expression of reporter gene under the control of AP-1/TPA response elements. We have also examined the possibility that ginsenoside Rc and Re act by binding to intracellular steroid hormone receptors that act as transcriptional factors in the nucleus in inducing c-fos mRNA in MCF7 human breast carcinoma cells. However, ginsenoside Rc and Re did not bind to glucocorticoid, androgen, estrogen, or retinoic acid receptors as examined by the transcription activation of the luciferase reporter genes in CV-1 cells that were transiently transfected with the corresponding steroid hormone receptors and hormone responsive luciferase reporter plasmids. These data demonstrate that ginsenoside Rc and Re act via other transcription factors and not via estrogen receptor in c-Fos expression.