• 한국수정란이식학회:학술대회논문집
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• 한국수정란이식학회 2002년도 국제심포지엄
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• pp.112-112
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• 2002

Under normal conditions, women produce a single dominant follicle that participates in a single ovuation each menstrual cycle. But Polycystic ovary syndrome(PCOS) conditions, folliculogenesis does not proceed normally. This condition leads to the accumlation of large numbers of small graffian follicles in which the theca interstitial cells (TIC) produce abnormally large amounts of androgen. PCOS is probably the most common endocrine disorder, affecting women of reprodutive age with 5-10% prevalence estimate. Chronic anovulation, hyperandrogenism, hirsutism, obesity, infertility and polycystic ovaries are clinical hallmarks of women with PCOS. Its etiology remains unknown. To investigate the gene expression pattern of ovary in PCO-induced rat, we used cDNA expression analysis. Total RNA was extracted from the ovary of PCO-induced rat and reverse-transcribed in the presence of［$\alpha$$^{32}$P］-dATP Which were hybridized to Atlas$^{TM}$ Rat Toxicology 1.2 array (Clontech) representing approximately 1176 rat genes. We compared gene expression between ovary of pco-induced immature female rats and control. Differential gene expression profiles were revealed (LIFR-alpha, ADRA1A, Heat shock 90-kDa protein A, PDGFRA). Reverse transcription-polymerase chain reaction(RT-PCR) was used to validate the relative expression pattern obtained by the cDNA array. The precise relationship between the altered expression of genes and PCO is a matter of further investigation. This study was supported by Korea Science and Engineering Foundation(KOSEF)

• Annals of Clinical Neurophysiology
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• 제4권1호
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• pp.51-55
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• 2002

Background : An increased frequency of reproductive endocrine disorders and polycystic ovary(PCO) has been reported in women with epilepsy. A possible role of the seizure disorder or, of the use of antiepileptic drugs(AEDs) has been suggested as the pathogenic mechanism. The objective of the present study was to assess the prevalence of reproductive endocrine disorders, such as PCO or menstrual abnormalities, in a series of women with epilepsy, examining the possible relationships of these disturbances with different epilepsy syndromes and AED treatment. Methods : Thirty epileptic women, all of reproductive age and none pubertal, pregnant, or lactating, were evaluated by clinical endocrinological assessment, and pelvic ultrasonography. Seven patients were on valproic acid(VPA), nineteen on carbamazepine(CBZ), and four on diphenylhydantoin(DPH) treatment, respectively. Results : Menstrual irregularity was observed in 8 women(26.7%), dysmenorrhea in 7(23.3%), and premenstrual syndrome in 1(3.3%). Ultrasonographic examination revealed that one women(3.3%) showed polycystic ovary, 4(13.3%) had ovarian cyst(s), and 2(6.7%) had uterine myoma, respectively. There was no difference in the prevalence of menstrual abnormalities or polycystic ovary according to the different preparations of AEDs. Conclusions : Data from this investigation suggest that, in Korean reproductive age women, the treatment of AEDs and the kind of medication may not have a significant effect on the prevalence of menstrual abnormalities or ultrasonographic polycystic ovary.

• 대한한방부인과학회지
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• 제23권4호
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• pp.35-46
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• 2010

Purpose: This study was designed to investigate the effects of Cyperi Rhizoma (CR) on changes in weights morphological and histopathological observations in Polycystic Ovary(PCO) rats. Methods: PCO was induced by single intramuscular injection with EV(2mg) in female rats. Normal group(n=8) were injected with sesame oil and orally administrated distilled water for five weeks. PCO control group(n=8) were injected with EV and orally administrated distilled water for five weeks. CR treated group(n=8) were injected with EV and orally administrated CR for five weeks. Then we measured weight of body, ovaries. The histopathology changes of ovaries, and the expression of nerve growth factor(NGF) were also evaluated. Results: Single injection of EV induced suppression of weight gain, formation of cysts, increase of NGF expression. Oral administration of CR prevent suppression of weight gain shown in control group. In addition CR group showed upward tendency of ovarian size. Formation of cystic follicles induced by EV injection is suppressed by CR treatment. In additon, CR treatment lowered expression levels of nerve growth factor(NGF), which were elevated by induction of PCOS. Conclusion: These results suggest that CR can be used for patients with PCOS to prevent formation of cystic follicles and malfunction of ovary. And also suggest that the related mechanisms are involved in suppression of NGF expression.

• 대한한방부인과학회지
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• 제21권3호
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• pp.60-74
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• 2008

Purpose: This study was designed to investigate the effects of Gwibi-Tang(GBT) on the polycystic ovary(PCO) induced by estradiol valerate(EV) in rats. Methods: PCO was induced by single intramuscular injection with EV(4mg) in female rats. Normal group(n=8) were injected with sesame oil and orally administrated distilled water for eight weeks. PCO control group(n=8) were injected with EV and orally administrated distilled water for eight weeks. GBT treated group(n=8) were injected with EV and orally administrated GBT for eight weeks. Then we measured weight of body, ovaries, adrenal glands, and uterus of rats. The histopathology changes of ovaries were also evaluated. The expression of nerve growth factor(NGF) was analyzed in the central nervous system, adrenal glands and ovaries by immunohistochemistry. And also CRF expression in median eminance of Rats were analyzed. Results: 1. The weight(g) of rats in GBT treated group($275{\pm}14$) was significantly increased(p<0.01) compared with control group($253{\pm}8$), 2. The weight(mg) of ovaries in GBT treated group($75.8{\pm}16.7$) was significantly increased(p<0.001) compared with control group($37.4{\pm}6.7$). 3. The number of mature follicles in GBT treated group($3.6{\pm}1.2$) was significantly increased(p<0.01) compared with control group($1.5{\pm}1.5$. 4. The number of atretic follicles in GBT treated group($8.0{\pm}3.1$) was significantly decreased(p<0.01) compared with control group($18.6{\pm}6.0$). 5. The number of cystic follicles in GBT treated group($0.5{\pm}0.5$) was significantly increased(p<0.01) compared with control group($2.3{\pm}1.3$). 6. The number of corpora lutea in GBT treated group($6.1{\pm}3.9$) was significantly increased(p<0.01) compared with control group($1.6{\pm}2.3$). 7. The expression of NGF-immunoreactive cells in the ovarian granulosa cells in GBT treated group was lesser observed than control group. Conclusion: From the above results, we concluded that Gwibi-Tang has inhibitory effect on the development of EV-induced polycystic ovary. And it's effect may be related with decreased NGF activities in the ovary.

• Clinical and Experimental Reproductive Medicine
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• 제25권1호
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• pp.93-102
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• 1998

Normal and abnormal follicular growth and steroidogenesis depend on gonadotropins as well as intraovarian peptides, which may mediate or potentiate gonadotropin action. Inhibin also affect follicular development and steroidogenesis and may play a role in dominant follicle selection and follicular atresia. Therefore, we studied the differences of serum inhibin, gonadotropin and androgen levels in the women with only the ultrasound findings and no disorder, and polycystic ovary (PCO) with ovulatory disturbance. We prospectively analysed forty-three women with PCO. The diagnosis of PCO was based on typical appearance of the ovaries on TVS. Twelve women with regular menstrual cycle and normal ovarian morphology were selected as control. Basal levels of inhibin, luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol $(E_2)$, testosterone (T), androstenedione (ADD), dehydroepiandrosterone-sulfate (DS), prolactin and TSH in serum were determined. There were significant differences in basal LH levels and LH/FSH ratio between the control and the women with PCO. The basal levels of inhibin and $E_2$ in the oligo-amenorrheic PCO (N=34) were significantly higher than those in the control. There was higher negative correlation between the inhibin and T levels in the oligo-amenorrheic PCO, but, not in the regular cycling PCO. Also, there was higher positive correlation between the LH and T levels in the oligo-amenorrheic PCO, but not in the regular cycling PCO. These data presume that the initial event of PCO is elevated pituitary LH secretion. Elevated levels of LH may down-regulate LH receptors on granulosa cells and also cause hypertrophy of the thecal layer. High level of androgen secreted by the hypertrophied thecal layer may stimulate inhibin secretion from granulosa cells and can be converted to estrogen by extraovarian tissues and could serve to augment pituitary sensitivity to GnRH with a resultant secretion of more LH than FSH. Inhibin may inhibit FSH action on granulosa cell in the PCO follicle, impairing follicular development and dominant follicle selection resulted in ovulatory disturbance.

• Applied Microscopy
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• 제41권2호
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• pp.109-116
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• 2011

다낭성 난소증후군(polycystic ovary syndrome, PCOS)은 내분비 및 대사장애로 호르몬 불균형 상태를 야기하여 가임기 여성의 불임 및 여러 합병증을 유발한다. 폐경기 여성의 호르몬대체 치료에 사용되는 estradiol valerate (EV)는 과다 투여 시 PCOS를 유발하는 것으로 알려졌다. 신경성장인자(nerve growth factor, NGF)는 발생 중인 신경세포의 생존과 성숙을 조절하는 인자로 난소에서도 합성되고, EV 처리에 의해 유도된 다낭성난소(polycystic ovary, PCO)에서 발현이 크게 증가하는 것으로 보고됐다. 따라서 본 연구에서는 난소유래 세포인 CHO 세포주와 다낭성 난소를 이용해 호르몬 불균형 상태인 PCOS 진단 시 NGF가 생물학적 표지인자로서 사용될 수 있는 가능성을 규명하고자 하였다. CHO 세포에 EV 2 mg과 3 mg 처리는 초기에 세포증식을 억제했으나 1 mg 처리는 영향을 미치지 않음으로써 실험 시 최적농도로 사용하였다. 하지만 농도별 EV 처리에 따른 CHO 세포의 형태학적 차이는 관찰되지 않았다. CHO 세포에 EV 처리 후 NGF mRNA 및 단백질 발현은 대조군에 비해 30분 후 크게 증가하였고, 다수의 난포낭이 관찰된 PCOS 조직에서도 정상군에 비해 크게 증가하였다. 따라서 이상의 결과들을 종합하면 EV 처리 후 난소에서 유도되는 NGF 과발현은 비정상적 난포발달을 유도하는 인자로 작용할 것으로 보이며, 다낭성난소 진단 시 표지인자로서 사용될 수 있을 것으로 생각된다.

• Applied Microscopy
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• 제39권1호
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• pp.1-7
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• 2009

사람에서의 PCO와 몇몇 측면에서 유사한, 실험적으로 유발된 다낭성난소(polycystic ovary, PCO)는 장기간 작용하는 estradiol valerate (EV)에 의해 유발된다. 랫드에서 스테로이드로 유발한 PCO 모델에서 홍삼 총사포닌의 역할에 대한 우리의 이전연구는 전침이 난소의 nerve growth factor (NGF) 농도를 조절하는 것을 검증하였다. 실제로 PCO와 관련된 난소 기능부전의 병리기전에서 신경성 요소의 관련성은 난소로의 교감신경유출(sympathetic outflow)의 증가로 인해 높아진다. 따라서 본 연구에서는 치료제로서의 GTS 투여가 PCO를 유발한 랫드에서 교감신경 활성을 조절할 것이라는 가설을 시험해보고자 하였다. 본 연구에서는 스테로이드로 유발한 PCO에 내재하고 있는 병태생리학적 과정과 연관된 NGF 단백질과 NGF mRNA를 분석함으로써 이루어졌다. PCO가 유발된 랫드에서 EV 대조군은 oil 대조군과 비교하였을 때 유의적으로 높은 NGF mRNA의 발현을 나타내었으며, GTS 투여군은 EV 대조군에 비해 유의적으로 낮은 NGF mRNA의 발현을 나타내었다. 그러나 NGF 단백질은 oil 대조군에 비해 EV 대조군과 GTS 투여군에서도 유의적인 변화를 발견할 수 없었다. 이러한 결과는 EV가 설치류에서 낭종 형성과 무배란을 유발하는 병리학적 단계의 구성요소일 수 있는 난소의 신경향성 단계(neurotrophic state)를 조절한다고 생각할 수 있다.

• Clinical and Experimental Reproductive Medicine
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• 제21권3호
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• pp.227-232
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• 1994

In order to define the clinical characteristics of Korean women with polycystic ovary syndrome, clinical symptoms, biochemical features and ultrasonographic findings were determined in ninety PCO patients. Frequency of clinical manifestations were as follows:acne 42%, overweight 31 %, oily skin 14 %, hirsutism 10%. Relatively low frequencies of hirsutism is recognized in patients with Korean PCO syndrome. Mean(${\pm}$S.E.) of each hormone was:testosterone 1.18${\pm}$1.07ng/ml, LH 21.47${\pm}$${\pm}$2.6mIU/ml, FSH 7.26${\pm}$2.67mIU/ml, LH/FSH ratio 2.94${\pm}$1.29, prolactin 25.48${\pm}$46.33ng/ml, DHEA-S 333.78${\pm}$309.60ng/dl, 17-0HP 1.72${\pm}$1.74ng/ml. Mean 17-OHP after ACTH stimulation test was 5.07${\pm}$12.01ng/ml. Ultrasonographically measured mean ovarian volume were $11.02{\pm}5.92cm^3$ in right and $9.23{\pm}5.64cm^3$ in left and small sized multiple subcapsular follicular cysts were noted in 43 patients (47.9%) with PCO syndrome.

• 한국임상수의학회지
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• 제28권4호
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• pp.403-407
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• 2011

A form of polycystic ovary (PCO) resembling some aspects of the human PCO syndrome (PCOS) can be induced in rats by a single injection of estradiol valerate (EV). An increase in sympathetic outflow to the ovary precedes, by several weeks, the appearance of cysts, suggesting the involvement of a neurogenic component in the pathology of this ovarian dysfunction. To test the hypotheses that the change in sympathetic tone is related to an augmented production of hippocampal and/or ovarian nerve growth factor (NGF), and that this abnormally elevated production of NGF contributes to the induction of PCOS induced by EV. The animals were sacrificed after PCOS induction and the ovaries and hippocampus were sectioned and compared to the normal control. The expression of NGF was measured by immunohistochemical staining and Western blot analysis in the ovaries and hippocampus. EV-induced PCOS showed significant increase of ovarian NGF expression. Immunohistochemical expression of NGF was confined to the follicular cells and interstitial cells. Hippocampal NGF expression was not significantly changed. In conclusion EV-induced PCOS was related to the ovarian sympathetic activation which was mediated by NGF.

• 대한한방부인과학회지
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• 제24권3호
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• pp.48-72
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• 2011

Objectives: This study was designed to investigate the effects of Yongdamsagantang on the polycystic ovary(PCO) induced by estradiol valerate(EV) in rats. Methods: After administrating Yongdamsagan-tang to PCO induced rats, we measured the weight of body, ovaries, adrenal glands, and uterus of rats. The observation through naked eye and histopathological observation of ovaries were evaluated. Also, the number of follicle and corpora lutea and content of androstenedione(ADD) and total estrogen were evaluated. The expressions of nerve growth factor(NGF) and corticotropin releasing factor(CRF) were analyzed by immunohistochemistry. The breeding rate and number of implantation with normal male rats were evaluated. Results: - The weight(mg) of ovaries in YST treated group($73.8{\pm}7.6$) was significantly increased(p<0.001) compared with control group($54.3{\pm}4.5$). - The number of mature follicles in YST treated group($7.3{\pm}2.4$) was significantly increased(p<0.01) compared with control group($3.5{\pm}1.2$). - The number of atretic follicles in YST treated group($9.0{\pm}1.5$) was significantly decreased(p<0.01) compared with control group($13.4{\pm}3.8$). - The number of cystic follicles in YST treated group($3.1{\pm}1.1$) was significantly decreased(p<0.01) compared with control group($6.0{\pm}2.0$). - The number of corpora lutea in YST treated group($3.8{\pm}2.1$) was significantly increased(p<0.001) compared with control group($0.3{\pm}0.7$). - The expression of NGF-immunoreactive cells in the ovarian granulosa cells in YST treated group was lesser observed than control group. - The expression of NGF-immunoreactive cells in the adrenal cortex in YST treated group was lesser observed than control group. - The breeding rate in YST treated group(100 %) was significantly increased (p<0.05) compared with control group(50 %). - The number of implantation in YST treated group($6.4{\pm}4.7$) was significantly increased(p<0.05) compared with control group($1.4{\pm}2.6$). Conclusions: We concluded that Yongdamsagan-tang activates the maturation of follicles, normal ovulation, breeding rate and number of implantation. Therefore, this may be effective for the treatment of anovulation, amenorrhea and sterility of PCOS patients.