• Journal of Genetic Medicine
• /
• 제17권1호
• /
• pp.1-10
• /
• 2020

Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder in women, which is characterized by the oligo/anovulation, hyperandrogenism (HA) and polycystic ovarian morphology which are diagnostic criteria. PCOS has diverse clinical aspects in addition to those diagnostic criteria including increased risk for cardiovascular diseases, metabolic syndrome, dyslipidemia, type 2 diabetes and impaired fertility. Because of the heterogeneity of the disease, the pathogenesis of the disease has not been elucidated yet. Therefore, there is no cure for the endocrinopathy. HA and insulin resistance (IR) has been considered two major pillars of the pathogenesis of PCOS. Recent advances in animal studies revealed the critical role of neuroendocrine abnormalities in developing PCOS. Several pathways related to neuroendocrine origin have been investigated such as hypothalamus pituitary ovarian axis, hypothalamus pituitary adrenal axis and hypothalamus pituitary adipose axis. This review summarizes the current knowledge about the role of HA and IR in developing PCOS. In addition, we review the results of recent genome wide association studies for PCOS. This new perspective improves our understanding of the role of neuroendocrine origins in PCOS and suggest a novel potential therapeutic target for the treatment of PCOS.

• 한국해양생명과학회지
• /
• 제1권1호
• /
• pp.41-49
• /
• 2016

Kisspeptin (Kiss) and its cognate receptor, kisspeptin receptor (KissR; G protein coupled receptor 54, GPR54), have recently been recognized as potent regulators of reproduction in teleosts. Additionally, leptin plays an important role in energy homeostasis and reproductive function in teleosts. The purpose of this study was to examine differences in the concentration of the hormones of the Kiss/KissR system and leptin and the expression of their underlying genes, all of which are involved in the sexual maturation of female goldfish, Carassius auratus, following treatment with Kiss. The expression levels of KissR increased after the Kiss injection. Furthermore, the peptide hormone leptin also increased after the injection (in vivo and in vitro). Additionally, the expression of GnRH and GTHs (GTHα, FSHβ, and LHβ) increased in the brain and pituitary (in vitro and in vitro). These results support the hypothesis that Kiss plays important roles in the direct regulation of the hypothalamus-pituitary-gonad axis and leptin in goldfish. Therefore, we suggest that Kiss system gene expression is correlated with energy balance and reproduction.

• Clinical and Experimental Reproductive Medicine
• /
• 제33권1호
• /
• pp.15-23
• /
• 2006

목 적: 본 연구는 흰쥐 난소를 실험모델로 하여 미성숙 전동 난포의 성장에 대한 pituitary adenylate cyclase-activating polypeptide (PACAP)의 영향을 얄아보고자 하였다. 연구방법: 미성숙 전동 난포를 생후 21일된 흰쥐로부터 분리하여 PACAP을 첨가하거나 첨가하지 않은 무혈청 배양액에서 3일 동안 배양하고, 푸로게스테론 호르몬의 생성, 난포의 성장, 과립막세포의 증식 및 유전자의 동태 등을 관찰하였다. 증식의 정도는 thymidine incorporation 방법으로 검색하고 유전자의 변동은 Northern 분석을 이용하였다. 결 과: PACAP으로 처리한 군은 난포의 직경이 75% 증가한 반면 난포자극호르몬인 FSH로 처리한 군은 65% 증가하였고, PACAP 처리는 과립막 세포의 증식을 강화시켰다. FSH와 PACAP 공히 배양된 흰쥐 난포의 과립막 세포와 FSH에 반응하는 세포주인 GFSHR-17에서의 프로게스테론 생성을 촉진시켰고, PACAP이 FSH의 작용을 증진시켜 SF-1과 아로마타제 유전자 발현을 촉진시켰다. 결 론: 본 연구는 PACAP이 과립막증식과 스테로이드합성을 통하여 전동 난포의 성장을 촉진함을 시사하였고, 또한, SF-1, 아로마타제 등에 대한 FSH의 작용을 도와주는 역할을 PACAP이 담당하므로 PACAP은 초기 난포성장에 필요한 난소국소인자임을 유추할 수 있었다.

• Journal of Korean Neurosurgical Society
• /
• 제30권5호
• /
• pp.567-574
• /
• 2001

Objective : As for growth hormone(GH) secreting pituitary adenoma, it's remission should be declared on the basis of satisfactory controlling of the tumor, normalization of hormonal level, and symptomatic improvement of the patient. Several modalities of treatment have been applied and administered, and yet, this disease still remains as inveterate one to be fully treated. The purpose of this study is to evaluate the outcome of gamma knife radiosurgery(GKRS) for GH secreting pituitary adenoma, and to identify various factors affecting the outcome of the treatment. Method : A group of 24 out of 35 patients, treated by Leksell gamma knife unit during the period of March of 1992 through October of 1997, had been observed for more than two years. The mean target volume of microadenoma was $449.3mm^3(range 216-880mm^3)$, and that of macroadenoma was $3183.1mm^3(range 1456-13125mm^3)$. The tumor margin was covered with 50% isodose profile, and mean marginal dose was 25.2Gy(range 15-32.4Gy). The mean number of isocenter was 4.3(range 1-6). The exposed dose to the optic apparatus was less than 8Gy. The mean follow-up period was 37.8months(range 24-102months). Result : No patients showed any increase in the tumor volume during the follow-up period. And definite shrinkage of tumor volume(tumor volume reduction rate, TVRR : more than 50%) was obtained in 10 patients(41.7%). Twenty one patients(87.5%) had reduced hormonal level compared than pre-treatment level. Among them, normalization of the hormonal level was achieved in 12 patients(50%). Clinicoendocrinological remission was seen in 3 patients (12.5%). According to the results of statistical analysis, tumor volume(p=0.016),duration of symptoms(p=0.046), initial GH level(p=0.017), and the invasion of cavernous sinus(p=0.036) were significantly favorable to post-radiosurgical outcome. The TVRR was significantly related to post-radiosurgical reduction of serum GH level. Permanent complication was not seen. Conclusion : The authors concluded that GKRS is a safe and effective treatment modality for acromegaly. To otain the better outcome of GKRS in GH secreting pituitary adenoma, more careful and sophisticated treatment-planning is recommended.

• Journal of Korean Neurosurgical Society
• /
• 제59권6호
• /
• pp.577-583
• /
• 2016

Objective : The inter-rater reliability of the modified Knosp's classification was measured before the analysis. The clinical validity of the parasellar extension grading system was evaluated by investigating the extents of resection and complication rates among the grades in the endoscopic endonasal transsphenoidal surgery (EETS) for pituitary adenomas. Methods : From November 2008 to August 2015, of the 286 patients who underwent EETS by the senior author, 208 were pituitary adenoma cases (146 non-functioning pituitary adenomas, 10 adrenocorticotropic hormone-secreting adenomas, 31 growth hormone-secreting adenomas, 17 prolactin-secreting adenomas, and 4 thyroid-stimulating hormone-secreting adenomas; 23 microadenomas, 174 macroadenomas, and 11 giant adenomas). Two neurosurgeons and a neuroradiologist independently measured the degree of parasellar extension on the preoperative sellar MRI according to the modified Knosp's classification. Inter-rater reliability was statistically assessed by measuring the intraclass correlation coefficient. The extents of resection were evaluated by comparison of the pre- and post-operative MR images; the neurovascular complications were assessed by reviewing the patients' medical records. The extent of resection was measured in each parasellar extension grade; thereafter, their statistical differences were calculated. Results : The intraclass correlation coefficient value of reliability across the three raters amounted to 0.862. The gross total removal (GTR) rates achieved in each grade were 70.0, 69.8, 62.9, 21.4, 37.5, and 4.3% in Grades 0, 1, 2, 3A, 3B, and 4, respectively. A significant difference in the extent of resection was observed only between Grades 2 and 3A. In addition, significantly higher complication rates were observed in the groups above Grade 3A. Conclusion : Although the modified Knosp's classification system appears to be complex, its inter-rater reliability proves to be excellent. Regarding the clinical validity of the parasellar extension grading system, Grades 3A, 3B, and 4 have a negative predictive value for the GTR rate, with higher complication rates.

• Journal of Korean Neurosurgical Society
• /
• 제29권6호
• /
• pp.754-762
• /
• 2000

Objectives : The surgical results of 80 patients with growth hormone(GH)-producing pituitary adenoma were analyzed retrospectively to evaluate the clinical manifestations and to determine which preoperative factors significantly influenced the surgical outcome. Patients and Methods : The patients consisted of 39 men and 41 women and the age of patients at the time of initial operation ranged from 17 to 67 years(mean age, 40.5 years) Between January 1990 and June 1996, 77 patients underwent transsphenoidal surgery and 3 patients underwent craniotomy for GH-producing pituitary adenoma at our institution. Preoperative administration of octreotide was performed in 18 patients. Surgical control was defined as a postoperative serum basal level of GH less than 5ng/ml. A logistic regression model was used for univariate and multivariate analysis. Probability value of less than 0.05 was considered as statistically significant. Results : The most common presenting symptom was acromegaly, followed by headache, visual disturbance, and fatigability. Visual symptoms were present in 39% of the patients. Diabetes mellitus was associated in 24 patients and hypertension in 12. Preoperative mean basal level of GH was 93.2ng/ml(range 72-500ng/ml) which was closely related with tumor size(p<0.05). Grade II by Hardy's classification was the most common radiological type. Preoperative octreotide treatment significantly reduced the level of GH(p<0.05), but not enough to induce endocrinological remission. One patient died of cerebral infarction after craniotomy. The most common surgical complication was transient diabetes insipidus. The symptom of the earliest improvement after surgery was paresthesia and tightness of the hand and foot, followed by headache and easy fatigability. The preoperative visual symptom was improved in all patients. The patients who had hypertension or DM experienced alleviated symptoms in 67% and 92%, respectively. The overall rate of endocrinological remission was 44%. By multivariate logistic regression analysis, the size of tumor, extrasellar extension, and extent of removal were significant prognostic factors for endocrinologial remission. Conclusion : Early detection of a small tumor without extrasellar extension followed by a complete resection is highly recommended in order to achieve endocrinological cure of GH-producing pituitary adenomas.

• 한국발생생물학회지:발생과생식
• /
• 제2권1호
• /
• pp.21-27
• /
• 1998

본 연구에서는 흰쥐 자궁에서 pituitary adenylate cyclase-activating polypeptide (PACAP)과 그 수용체 유전자들이 발현되는가와 각각 어떠한 유형의 transcript들이 발현되는가를 조사하였고, 이를 위해 역전사 중합효소 연쇄반응 (RT-PCR)을 시행하였다. 시상하부와 정소에서 공통적으로 존재함이 알려진 PACAP common exon 부위에 해당되는 primer를 사용하여 PCR을 시행한 결과 자궁을 포함한 모든 조직에서 에상대로 297 bp의 band가 확인되었다. 흰쥐 자궁에서 발현되는 PACAP mRNA에 정소 특이적인 exon 1이 포함되는가를 조사하기 위해 정소 특이적인 primer를 사용하여 PCR을 시행한 결과, 정소에서만 예상대로 586 bp의 band가 검출되었고 자궁을 포함한 다른 조직에서는 발견되지 않았다. 흰쥐의 PACAP 수용체 PCR에서는 자궁에서 923 bp와 839 bp크기의 band를 확인할 수 있었으며, 이는 알려진 PACAP type I수용체의 splicing variant 들 가운데 hip-hop (923bp)과 hip- 또는 nop-type (839bp)의 예상 크기와 일치하였다. 인위적으로 성적인 성숙을 유도한 PMSG 주사모델하에서 자궁내 PACAP transcript 수준은 주사 24 시간 후 실험군에서 증가하여 생식주기상 proestus 시기에 해당되는 주사 48 시간까지 증가하였다가 72 시간후에는 control 보다 낮은 수준을 보였는데, 이는 자궁의 PACAP 유전자발현이 생리적으로 조절됨을 나타내는 것이다. 본 연구는 흰쥐의 자궁에서 PACAP과 그 수용체 isoform들의 유전자가 발현됨을 최초로 보고한 것으로 자궁 자체에서 발현되는 PACAP이 autocrine 또는 paracrine하게 자궁의 생리 및 기능 조절을 담당함을 시사한다.

• Journal of Korean Neurosurgical Society
• /
• 제67권2호
• /
• pp.237-248
• /
• 2024

Objective : Postoperative data on Cushing's disease (CD) are equivocal in the literature. These discrepancies may be attributed to different series with different criteria for remission and variable follow-up durations. Additional data from experienced centers may address these discrepancies. In this study, we present the results obtained from 96 endoscopic transsphenoidal surgeries (ETSSs) for CD conducted in a well-experienced center. Methods : Pre- and postoperative data of 96 ETSS in 87 patients with CD were included. All cases were handled by the same neurosurgical team between 2014 and 2022. We obtained data on remission status 3-6 months postoperatively (medium-term) and during the latest follow-up (long-term). Additionally, magnetic resonance imaging (MRI) and pathology results were obtained for each case. Results : The mean follow-up duration was 39.5±3.2 months. Medium and long-term remission rates were 77% and 82%, respectively. When only first-time operations were considered, the medium- and long-term remission rates were 78% and 82%, respectively. The recurrence rate in this series was 2.5%. Patients who showed remission between 3-6 months had higher long-term remission rates than did those without initial remission. Tumors >2 cm and extended tumor invasion of the cavernous sinus (Knosp 4) were associated with lower postoperative remission rates. Conclusion : Adenoma size and the presence/absence of cavernous sinus invasion on preopera-tive MRI may predict long-term postoperative remission. A tumor size of 2 cm may be a supporting criterion for predicting remission in Knosp 4 tumors. Further studies with larger patient populations are necessary to support this finding.

• 한국발생생물학회지:발생과생식
• /
• 제11권1호
• /
• pp.49-54
• /
• 2007

Ethane 1,2-dimethane sulfonate(EDS)은 Leydig cells(LC)만을 선별적 사멸을 유도하는 약물로서 가역적인 테스토스테론(testosterone, T) 결핍 흰쥐 모델을 만드는데 널리 사용된다. 본 연구에서는 수컷 흰쥐 뇌하수체의 생식소자극호르몬인 LH와 FSH의 발현에 미치는 EDS 투여 효과를 조사하였다. 성숙한 수컷 흰쥐(SD strain, $300{\sim}350\;g$ B.W.)에 EDS(75 mg/kg, i.p.)를 1회 복강주사하고 주사 후 0, 1, 2, 3, 4, 5, 6 그리고 7주가 경과한 날 희생시켰다. 뇌하수체로부터 total RNA를 추출한 후 뇌하수체 glycoprotein hormone common alpha subunit($C{\alpha}$), LH beta subunit($LH{\beta}$), FSH beta subunit($FSH{\beta}$) 그리고 GnRH 수용체(GnRH-R)의 발현 변화를 semi-quantitative RT-PCR로 측정하였다. 그 결과, $C{\alpha}$ 전사수준은 주사 후 1주부터 급격히 상승하여 주사 후 4주까지 유의하게 높게 유지되다가 5주 후부터 control 수준으로 회귀하였다. $LH{\beta}$ 전사 수준은 주사 후 2주부터 유의하게 상승하여 주사 후 4주에 최고 수준에 도달하였으며, 5주 후부터 control 수준으로 감소하였다. $FSH{\beta}$ 전사수준은 주사 후 2주부터 유의하게 상승하여 주사 후 3주에 최고 수준에 도달하였으며, 4주 후부터 감소하여 5주 후에 최소치를 보였다. 유사하게, GnRH-R 전사 수준도 주사 후 2주부터 유의하게 상승하여 주사 후 3주에 최고 수준에 도달하였으며, 5주 후부터 control 수준으로 감소하였다. 본 연구는 EDS 주사에 의해 수컷 흰쥐 뇌하수체 전엽에서의 생식소 자극호르몬 subunit들과 GnRH-R의 발현 변화가 가역적으로 유도될 수 있음을 보여준 것이다. EDS 주사 모델은 수컷 흰쥐에서의 시상하부-뇌하수체 신경내분비 축의 호르몬 조절에 대한 기작을 이해하는데 도움이 될 것이다.

• 생물정신의학
• /
• 제3권2호
• /
• pp.288-294
• /
• 1996

전기경련요법을 시행받은 9명의 정동자애 환자들과 2명의 정신분분열형장애 환자들에서 각각 3분 간격으로 혈액을 채취하여 각 채취하여 AVF, ACTH, PRL, cortisol 등의 호르몬에 대해 기저농도 및 전기경련요법 후의 농도 변화를 측정함으로써 각 호르몬 분비 반응 사이의 시간적인, 그리고 양적인 관계를 비교분석하였다. 또한 경련 지속 시간과 각 호르몬 분비반응들 사이의 상관관계도 검토하였다. 상기 호르몬 모두에서 전기경련요법 대한 의미있는 분비반응이 관찰되었다. 즉, AVP는 1.2pg/ml에서 33.3pg/ml(P<0.001). PRL은 21.8ng/ml에서 102.2ng/ml(P<0.005)로 cortsol은 20.1ug/dl에서 31.1ug/dl(P<0.001)로 각각 중가 되었다. 뇌하수체에서 분비되는 AVP, ACTH, PRL 세가지 호르몬 모두는 전기경련 요법 후 3분내에 분비 반용이 시작되었지만, 최고 농도에 도달하는 시간은 각각 3분, 6분, 12~15분대로 분명히 구별되는 소견을 보였다. cortisol은 6분후부터 증가하기 시작하여 20~30분 사이에 최고 농도를 보였다. 경련 지속 시간과 분비 반응과는 의미있는 상관관계를 보이지 않았다. 이상의 연구결과를 토대로 저자들은 다음과 같은 결론에 도달하였다. 1) 전기경련 요법에 대한 뇌하수체 호르몬의 반응은 동시적이라기 보다는 순차식으로 일어나는 것이다. 2) AVP는 다른 어떤 호르몬 보다도 아주 빠르고 양적으로 많은 반응을 보였다. 3) AVP 반응 후에 뒤따르는 ACTH 반응은 대부분의 과거 연구들에서 보고된 것보다 빠르고 강력했다. 4) 이러한 결과들은 뇌하수체 호르몬이 전기 자극보다는 경련의 결과로 분비된다는 가설을 지지해 주는 소견이다. 5) 시상하부-뇌하수체-부신피질 축 호르몬들의 순차적 반웅 양상은 각 호르몬의 분비 반응에 되먹임 조절 기전이 관여할 수 있음을 추정케 한다.