• 한방재활의학과학회지
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• 제30권1호
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• pp.1-12
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• 2020

Objectives Depletion of ovarian function after menopause in women induces estrogen deficiency leading to increased fat and decreased muscle mass. In this study, we examined the effect of herbal medicines by measuring hormone expression in muscle tissue of estrogen-deficient rats induced by ovariectomy. Methods Ovariectomy was performed to induce estrogen deficiency, and mice were given herbal prescription (HP) for 6 weeks. Estrogen-deficient rats were divided into two groups: one group (HPH) which were orally administered HP 200 mg/kg and the other group (HPL) administered HP 40 mg/kg. Weight changes in both groups were measured using polymerase chain reaction (PCR). After extraction of the femoral muscles in mice, the expression of the leptin, lipoprotein lipase (LPL), diacyl glycerol acyltransferase (DGAT)1, peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α, NADH dehydrogenase (NDH), farnesyl diphosphate farnesyltransferase (FDFT)1, lanosterol synthase (LSS), phosphatidylethanolamine N-methyltransferase (PEMT), and peroxiredoxin (Prdx6) were measured using PCR. Results HP increased the expression of leptin, LPL, DGAT1, PGC-1α, NDH, FDFT1, LSS, PEMT, and Prdx6. HP affects body fat metabolism and is effective in improving menopausal obesity and obesity complications caused by estrogen deficiency. However, HP does not affect the expression of tumor necrosis factor-α and 3-hydroxy-3-methylglutaryl-CoA reductase, and thus will not be effective in obesity-related metabolic diseases. Conclusions HP is thought to inhibit weight gain by regulating hormone expression related to glucose metabolism and lipid metabolism in muscle tissue of estrogen-deficient rats.

• Clinical and Experimental Reproductive Medicine
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• 제43권4호
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• pp.207-214
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• 2016

Objective: This study aimed to determine the threshold of $anti-M{\ddot{u}}llerian$ hormone (AMH) as predictor of follicular growth failure in polycystic ovary syndrome (PCOS) patients treated with clomiphene citrate (CC). Methods: Fifty female subjects with PCOS were recruited and divided into two groups based on successful and unsuccessful follicular growth. Related variables such as age, infertility duration, cigarette smoking, use of Moslem hijab, sunlight exposure, fiber intake, body mass index, waist circumference, AMH level, 25-hydroxy vitamin D level, and growth of dominant follicles were obtained, assessed, and statistically analyzed. Results: The AMH levels of patients with successful follicular growth were significantly lower (p= 0.001) than those with unsuccessful follicular growth ($6.10{\pm}3.52$ vs. $10.43{\pm}4.78ng/mL$). A higher volume of fiber intake was also observed in the successful follicular growth group compared to unsuccessful follicular growth group (p= 0.001). Our study found the probability of successful follicle growth was a function of AMH level and the amount of fiber intake, expressed as Y =-2.35+($-0.312{\times}AMH\;level$)+($0.464{\times}fiber\;intake$) (area under the curve, 0.88; 95% confidence interval, 0.79-0.98; p< 0.001). Conclusion: The optimal threshold of AMH level in predicting the failure of follicle growth in patients with PCOS treated with CC was 8.58 ng/mL.

• Genomics & Informatics
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• 제3권4호
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• pp.154-158
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• 2005

Germ-line mutations of the BRCA1 gene confer an increased risk for breast and ovarian cancers. BRCA1 in female cells is directly related with the maintenance of the inactive X chromosome (Xi). The effect by the loss of the BRCA1 function on the X chromosome gene expression remains unclear in cancer cells. We attempted to investigate the expression pattern of the X-linked genes by performing BRCA1 knockdown via RNA interference in the MCF7 breast cancer cell line. The transcriptional and translational levels of BRCA1 were decreased over 95% in the MCF7 cells after BRCA1 knockdown. The expression patterns of one hundred ninety X-linked genes were profiled by the X chromosome-specific cDNA arrays. A total of seven percent of the X-linked genes (14/190) were aberrantly expressed by over 2-fold in the MCF7-BRCA1 knockdown cells, which contained two up-regulated genes (2/190, 1 %) and 12 down-regulated genes (12/190, 6.3%). It is interesting that 72% of the aberrantly expressed X-linked genes were located on the Xq (10/14,) region. Our data suggests that BRCA1 may not be important to maintain X chromosome inactivation in cancer because the BRCA1 knockdown did increase the expression of the only one percent of X-linked genes in the human breast cancer cells.

• Reproductive and Developmental Biology
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• 제42권2호
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• pp.7-12
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• 2018

In this review, we have tried to summarize the evidence and molecular characterization indicating that $20{\alpha}$-hydroxysteroid dehydrogenase ($20{\alpha}$-HSD) is a group of the aldo-keto reductase (AKR) family, and it plays roles in the modulation and regulation of steroid hormones. This enzyme plays a critical role in the regulation of luteal function in female mammals. We have studied the molecular expression and regulation of $20{\alpha}$-HSD in cows, pigs, deer, and monkeys. The specific antibody against bovine $20{\alpha}$-HSD was generated in a rabbit immunized with the purified recombinant protein. The mRNA expression levels increased gradually throughout the estrous cycle, the highest being in the corpus luteum (CL) 1 stage. The mRNA was also specifically detected in the placental and ovarian tissues during pregnancy. The $20{\alpha}$-HSD protein was intensively localized in the large luteal cells and placental cytotrophoblast villus, glandular epithelial cells of the endometrium, syncytiotrophoblast of the placenta, the isthmus cells of the oviduct, and the basal part of the primary chorionic villi and chorionic stem villus of the placenta and large luteal cells of the CL in many mammalian species. Further studies are needed to determine the functional significance of the $20{\alpha}$-HSD molecule during ovulation, pregnancy, and parturition. This article will review how fundamental information of these enzymes can be exploited for a better understanding of the reproductive organs during ovulation and pregnancy.

• 대한한방부인과학회지
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• 제32권3호
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• pp.192-213
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• 2019

Objectives: The purpose of this study is to analyze the domestic study trends of pharmacopuncture therapy on obstetrics and gynecological diseases in Korean literature, through reviewing the clinical and experimental studies. Methods: We searched for clinical and experimental studies using pharmacopuncture therapy on obstetrics and gynecological diseases, published from January 2000 to May 2019, through 5 Korean databases. The study design, target disease, type of pharmacopuncture, method of intervention, and study results were analyzed. Results: 36 experimental studies and 15 clinical studies were finally included according to inclusion and exclusion criteria. In experimental studies, there were 12 studies about postmenopausal osteoporosis, 9 studies about obesity, 4 studies about endometriosis, 3 studies about hemostatic effects and analgesic anticoagulative effects, 2 studies about ovarian function, and analgesic antiphlogistic anticoagulative effects, and 1 study about menopausal symptoms. In clinical studies, there were 3 studies about obesity, postpartum disorders, dysmenorrhea, and women's urologic disease, and 1 study about menopausal symptoms, atypical squamous cells of undetermined significance (ASCUS) and breast cancer. Various types of pharmacopuncture have been proved to have a therapeutic effect in each of those obstetrics and gynecological diseases. Conclusions: This study indicates that pharmacopuncture therapy could be a good treatment for obstetrics and gynecological diseases. However, more well-designed and high-quality clinical researches are needed in further studies, to prove the effectiveness and safety of pharmacopuncture therapy.

• 농업과학연구
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• 제48권1호
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• pp.163-170
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• 2021

Bacterial infections in the female reproductive tract negatively affect ovarian function, follicular development, and embryo development, leading to the eventual failure of fertilization. Moreover, bacterial lipopolysaccharides (LPS) can interfere with the immune system and reproductive system of the host animal. Therefore, this study examined the effect of LPS on the in vitro maturation (IVM) of pig oocytes. Oocytes were matured in TCM199 medium in the presence of varying concentrations of LPS (0 - 50 ㎍·mL^-1). The maturation rate, cortical granules (CGs) migration, and chromosome alignment were subsequently evaluated during the meiotic development of the oocytes. We observed a dose-dependent and significant decrease in the metaphase II (MII) rate with increasing concentrations of LPS (97.6% control [0 ㎍·mL^-1 LPS] vs. 10.4-74.9% LPS [1 - 50 ㎍·mL^-1], p < 0.05). In addition, compared to the control oocytes without LPS, higher levels of abnormal CGs distribution (18.1 - 50.0% LPS vs. 0% control), chromosome/spindle alignment (20.3 - 56.7% LPS vs. 0% control), and intracellular ROS generation were observed in oocytes matured with LPS (p < 0.05). Nitrite levels were also increased in the maturation medium derived from the oocytes matured with LPS (p < 0.05). These results indicate that LPS induces oxidative stress during IVM and affects oocyte maturation, including CGs migration and chromosome alignment of pig oocytes.

• 한국발생생물학회지:발생과생식
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• 제27권4호
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• pp.185-193
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• 2023

Although increasing evidence of cause-and-effect relationship between BPA exposure and female reproductive disorders have been suggested through many studies, the precise biochemical and molecular mechanism(s) by which BPA interferes with steroidogenesis in the ovarian cells still remain unclear. Therefore, the purpose of this study was to discover the steroidogenic biomarker(s) associated with BPA treatment in human granulosa cell line, KGN. In this study, our results obtained via the analysis of steroidogenesis-related protein expression in KGN cells using quantitative polymerase chain reaction (qPCR) and western blot analyses revealed that the expression levels of steroidogenic acute regulatory (StAR) and aromatase decreased considerably and gradually after BPA treatment in a dose-dependent manner under BPA treatment. Further, remarkable decreases in their expression levels at the cellular levels were also confirmed via immunocytochemistry, and subsequent StAR and aromatase mRNA expression levels showed profiles similar to those observed for their proteins, i.e., both StAR and aromatase mRNA expression levels were significantly decreased under BPA treatment at concentrations ≥0.1 μM. We observed that follicle stimulating hormone upregulated StAR and aromatase protein expression levels; however, this effect was suppressed in the presence of BPA. Regarding the steroidogenic effects of BPA on KGN cells, controversies remain regarding the ultimate outcomes. Nevertheless, we believe that the results here presented imply that KGN cells have a good cellular and steroidogenic machinery for evaluating endocrine disruption. Therefore, StAR and aromatase could be stable and sensitive biomarkers in KGN cells for the cellular screening of the potential risk posed by exogenous and environmental chemicals to female reproductive (endocrine) function.

• 한국발생생물학회지:발생과생식
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• 제6권2호
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• pp.123-129
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• 2002

비만유전자 산물인 leptin은 비만뿐만 아니라 여성의 생식 생리와 관련이 있는 것으로 보이나, 아직 이러한 leptin이 난소에 직접적으로 작용하는지 정확하게 밝혀지지 않고 있다. 따라서 본 연구에서는 흰쥐 난소에서 leptin과 leptin 수용체의 발현을 면역조직화학방법으로 확인하고 발정주기에 따른 leptin과 leptin 수용체의 발현 양상을 RT-PCR 방법으로 조사하고자 하였다. 면역조직화학적 염색방법 결과 흰쥐 난소내에서 leptin은 협막세포와 폐쇄 난포의 일부 과립세포에 염색되었고, leptin 수용체는 협막세포, 간질세포와 난포강이 형성되지 않은 난포의 난자에 염색되었다. 특히 폐쇄 난포에서는 leptin과 leptin 수용체가 정상 난포에 비해 강하게 염색되었다. 흰쥐의 발정주기 동안 혈청내 estradiol, progesterone leptin의 농도는 ELISA 방법으로 측정하였고, 난소내 leptin과 leptin 수용체의 mRNA 발현 양상은 RT-PCR 방법으로 조사하였다. 혈중 leptin 농도를 측정한 결과 estrous 시기에 비하여 metestrous 시기에 유의하게 증가하였고, 이 시기에 progesterone 농도가 함께 증가하는 것을 관찰할 수 있었다. Leptin mRNA는 모든 발정주기에서 발현되지 않았지만 leptin 수용체 mRNA는 diestrous 시기를 제외한 다른 발정주기에 모두 발현되었다. 이러한 결과는 leptin이 흰쥐 난소의 기능을 조절하는데 직접적으로 관여할 수 있다는 것을 제시하고 있다.

• 생명과학회지
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• 제26권7호
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• pp.826-834
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• 2016

본 연구는 Hsp90 inhibitor 및 SIRT1 inhibitor의 병용처리가 항암제 다제내성(MDR) 인간 암세포의 증식 억제에 효과적임을 밝혔다. SIRT1 활성 억제가 Hsp90 inhibitor인 17-AAG의 세포 독성의 효과를 증강시켰으며, 이로 인해 Hsp90 inhibitors에 대한 내성을 극복시킬 수 있음을 인간 자궁암세포인 HeyA8의 MDR 변이주인 HeyA8- MDR 세포에서 확인하였다. SIRT1 inhibitor는 Hsp90 inhibitor에 의한 Hsp90 샤페론 기능 억제를 증강시키며, ubiquitin ligase CHIP의 발현 증강을 유발하여, Hsp90 client protein 인 mutant p53 (mut p53)의 분해를 촉진시킨다. Mut p53 의 발현 감소는 암세포의 Hsp90 inhibitor 내성 획득의 가장 중요한 원인으로 지적되는 heat shock factor 1 (HSF1)/heat shock proteins (Hsps)의 발현 억제와 관련됨을 알 수 있었으며, 이는 항암제 다제내성 세포에서 SIRT1 inhibitor에 의하여 Hsp90 inhibitor에 대한 감수성이 증강되는 분자적 기전임을 밝혔다. 그러므로, SIRT1 억제에 의한 mut p53/HSF1 발현 감소가 MDR 암세포의 Hsp90 inhibitors 내성 극복에 매우 유효함을 시사하는 결과를 얻었다.

• 대한방사선치료학회지
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• 제33권
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• pp.145-153
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• 2021

목 적: 본 연구에서는 가임기 여성의 유방암 방사선 치료 시 난소 선량에 대해 실험을 통하여 평가해보고자 한다. 치료기법에 따른 치료계획시스템에서 계산된 선량과 열형광선량계를 이용한 측정선량을 비교·분석하여 난소 선량을 평가하고 납(Pb) 앞치마의 사용유무에 따른 선량 분석을 통해 임상에서의 유용성을 알아보고자 한다. 대상 및 방법: 측정에는 Rando humanoid phantom을 이용하였고, 치료기법으로는 쐐기필터치료기법, 3차원 입체조형치료, 세기변조방사선치료를 사용하였다. CT simulator를 이용하여 얻은 Rando humanoid phantom 3D 영상의 우측 유방에 처방선량의 95%가 전달될 수 있도록 치료계획을 세웠고, TLD를 Rando hunmanoid phantom의 가상 표적의 표면 및 심부에 삽입하고 방사선을 조사하였다. 측정위치는 치료 중심점과 Rando humanoid phantom의 정중앙을 중심으로 반대쪽 유방으로 2cm 이동한 지점과 치료 중심축 및 하방으로 우측 유방의 경계면에서 5cm, 10cm, 12.5cm, 15cm, 17.5cm, 20cm, 우측 난소 위치의 표면과 중심점을 포함하여 총 9개 지점에서 측정하였다. 치료계획시스템의 선량 비교에서는 쐐기필터치료기법 2가지와 3차원 입체조형치료, 세기변조방사선치료 등 총 4개의 치료 계획을 수립하여 비교하였다. 그리고 TLD를 이용한 측정값 비교는 세기변조방사선치료와 쐐기필터를 이용한 치료를 비교하였고, 납 앞치마의 사용유무에 따라서 세기변조방사선치료의 선량차이를 측정하여 비교·분석하였다. 측정값은 각 포인트마다 3개의 TLD값 평균을 내고 TLD 교정값을 이용하여 환산하였으며 이를 Point dose mean값으로 계산하였다. 치료계획값과 실제 측정값을 비교하기 위해 각 지점마다 절대선량값을 측정하여 %Diff 값으로 계산하였다. 결 과: 치료 중심점인 Point A에서는 치료계획시스템에서 최대 201.7cGy가 나왔고, 실제 TLD 측정값은 최대 200.6cGy가 나왔다. 모든 치료계획시스템에서 유방 경계면으로부터 하방으로 17.5cm 떨어진 지점인 Point G 부터는 0cGy로 계산이 되었다. 실제 TLD 측정 결과 Point G에서는 최대 2.6cGy가 나왔고, 난소선량인 Point J에서는 최대 0.9cGy로 나타났으며 %Diff값은 0.3%~1.3%였다. 납 앞치마의 사용유무에 따른 선량 차이는 최대 2.1cGy에서 최소 0.1cGy로 나타났으며 %Diff값은 0.1%~1.1%였다. 결 론: 치료계획시스템에서 3가지 치료계획에 따른 선량차이는 최저 0.85%에서 최고 2.45%로 큰 격차를 보이지 않았다. 난소에서 Rando humanoid phantom의 치료계획과 실제 측정한 선량차이는 0.9% 이내로 나타났으나 실제 측정에서 조금 더 높게 측정되었다. 이는 치료계획시스템에서 산란선의 영향을 정확하게 반영하지 못하였고, 실제 측정에서는 TLD를 삽입한 상태로 CBCT를 촬영한 선량과 산란선량이 반영된 것으로 사료된다. 납 앞치마의 유무에 따른 선량측정에서 납 앞치마를 사용했을 경우에 치료범위에서 가까운 거리일수록 차폐의 효과가 있었으며, 치료범위에서 15cm 이상 거리가 있는 경우에는 거의 영향을 미치지 않는 것으로 나타났다. 임상적으로 방사선 치료 중에는 임신이나 인공수정을 하기에는 적절하지 않지만, 치료 중 난소에 조사된 선량은 방사선 치료 후 가임기 여성의 생식 기능에 크게 영향을 주지 않을 것으로 생각된다. 하지만 가임 여성의 경우에는 지속적인 불안감을 가지고 있으므로 이번 결과를 통한 데이터를 제시함으로써 심리적인 안정을 도모할 수 있을 것으로 사료된다.