Expression of NGF in Estradiol Valerate-Induced Polycystic Ovary and CHO Cells

Estradiol Valerate에 의해 유도된 다낭성난소와 CHO세포에서 NGF발현

  • Choi, Baik-Dong (Department of Oral Histology and Developmental Biology, School of Dentistry, Chosun University) ;
  • Jeong, Soon-Jeong (Department of Oral Histology and Developmental Biology, School of Dentistry, Chosun University) ;
  • Jeong, Moon-Jin (Department of Oral Histology and Developmental Biology, School of Dentistry, Chosun University) ;
  • Lim, Do-Seon (Department of Dental Hygiene, Eulji University) ;
  • Lee, Soo-Han (College of Veterinary Medicine, Konkuk University) ;
  • Kim, Seung-Hyun (College of Veterinary Medicine, Chonnam National University) ;
  • Go, A-Ra (College of Veterinary Medicine, Chonnam National University) ;
  • Kim, Se-Eun (College of Veterinary Medicine, Chonnam National University) ;
  • Kang, Seong-Soo (College of Veterinary Medicine, Chonnam National University) ;
  • Bae, Chun-Sik (College of Veterinary Medicine, Chonnam National University)
  • 최백동 (조선대학교 치과대학 구강조직발생학교실) ;
  • 정순정 (조선대학교 치과대학 구강조직발생학교실) ;
  • 정문진 (조선대학교 치과대학 구강조직발생학교실) ;
  • 임도선 (을지대학교 치위생학과) ;
  • 이수한 (건국대학교 수의과대학) ;
  • 김승현 (전남대학교 수의과대학) ;
  • 고아라 (전남대학교 수의과대학) ;
  • 김세은 (전남대학교 수의과대학) ;
  • 강성수 (전남대학교 수의과대학) ;
  • 배춘식 (전남대학교 수의과대학)
  • Received : 2011.05.17
  • Accepted : 2011.06.22
  • Published : 2011.06.30

Abstract

Polycystic ovary syndrome (PCOS) is hormonal imbalance condition as the endocrine and metabolic disorder that induces the infertility and various complications in reproductive age women. Estradiol valerate (EV) is used hormone replacement therapy in menopausal women and is reported that excessive administration of EV induces the PCOS. Nerve growth factor (NGF) is the factor to regulate the survival and maturation of developing neuronal cell and is also synthesized in ovary. And NGF is overexpressed in EV-induced polycystic ovary (PCO) as previously reported. Therefore, this study examined the possibility of NGF as can be used the biological marker in diagnosis of PCOS, the hormonal imbalance condition, using PCO and CHO (chinese hamster ovarian) cell lines. The concentration of EV treatment is optimized a 1 mg as not influence on the proliferation of CHO cell but 2 mg and 3 mg of EV treatment have the inhibition effect at initial stage. The morphological change was not observed in CHO cell after dose dependent manner treatment of EV. Expression of NGF mRNA and protein is significantly increased at 30 min after EV treatment in CHO cells compared to that of control. And NGF protein expression is strongly increased in PCO tissue, which observed many follicular cysts compared to normal ovary tissue. Taken together, overexpression of NGF may be act as a molecule to induce an abnormal development of follicle, suggesting that NGF can be used as a biological marker in diagnosis of PCOS.

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.

Keywords

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