Applied Microscopy

Korean Society of Microscopy (한국현미경학회)
권호 표지

Studies on the Therapeutic Effect and Mechanism of Korean Red Ginseng Total Saponin on Infertility Caused by Polycystic Ovaries

홍삼사포닌 투여의 다낭성난소에 의한 불임 치료효과 및 기작연구

  • Kim, Se-Eun (College of Veterinary Medicine, Animal Medical Institute, Chonnam National University) ;
  • Oh, Dong-Min (College of Veterinary Medicine, Animal Medical Institute, Chonnam National University) ;
  • Sim, Kyung-Mi (College of Veterinary Medicine, Animal Medical Institute, Chonnam National University) ;
  • Jeong, Moon-Jin (Department of Oral Histology, College of Dentistry, Chosun University) ;
  • Lim, Sung-Chul (Department of Pathology and Research Center for Resistant Cells, College of Medicine, Chosun University) ;
  • Nah, Seung-Yeol (Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine, Konkuk University) ;
  • Lee, Yun-Lyul (Department of Physiology, Hallym University College of Medicine) ;
  • Kang, Seong-Soo (College of Veterinary Medicine, Animal Medical Institute, Chonnam National University) ;
  • Moon, Chang-Jong (College of Veterinary Medicine, Animal Medical Institute, Chonnam National University) ;
  • Kim, Jong-Choon (College of Veterinary Medicine, Animal Medical Institute, Chonnam National University) ;
  • Kim, Sung-Ho (College of Veterinary Medicine, Animal Medical Institute, Chonnam National University) ;
  • Bae, Chun-Sik (College of Veterinary Medicine, Animal Medical Institute, Chonnam National University)
  • 김세은 (전남대학교 수의과대학 및 동물의학연구소) ;
  • 오동민 (전남대학교 수의과대학 및 동물의학연구소) ;
  • 심경미 (전남대학교 수의과대학 및 동물의학연구소) ;
  • 정문진 (조선대학교 치과대학 구강조직학교실) ;
  • 임성철 (조선대학교 의과대학 병리학교실 및 내성세포연구센터) ;
  • 나승열 (건국대학교 수의과대학 생리학교실) ;
  • 이윤렬 (한림대학교 의과대학 생리학교실) ;
  • 강성수 (전남대학교 수의과대학 및 동물의학연구소) ;
  • 문창종 (전남대학교 수의과대학 및 동물의학연구소) ;
  • 김종춘 (전남대학교 수의과대학 및 동물의학연구소) ;
  • 김성호 (전남대학교 수의과대학 및 동물의학연구소) ;
  • 배춘식 (전남대학교 수의과대학 및 동물의학연구소)
  • Published : 2009.03.31
Download PDF
⟨ Previous Next ⟩

Abstract

Experimental induction of polycystic ovary (PCO) resembling some aspects of human PCO syndrome was produced using the long-acting compound estradiol valerate (EV). Our previous study on the role of Korean red ginseng total saponins (GTS) in a steroid-induced PCO rat model demonstrated that electro-acupuncture modulates nerve growth factor (NGF) concentration in the ovaries. In fact, the involvement of a neurogenic component in the pathology of PCO-related ovarian dysfunction is preceded by an increase in sympathetic outflow to the ovaries. In the present study, we tested the hypothesis that therapeutic GTS administration modulates sympathetic nerve activity in rats with PCO. This was done by analyzing NGF protein and NGF mRNA expression involved in the pathophysiological process underlying steroid-induced PCO. EV injection resulted in significantly higher ovarian NGF mRNA expression in PCO rats compared to control rats, and PCO ovaries were counteracted by GTS administration with significantly lower expression of NGF mRNA compared to EV treated ovaries. However, NGF protein was unaffected in both EV and GTS treated ovaries compared to control rats. These results indicate that EV modulates the neurotrophic state of the ovaries, which may be a component of the pathological process by which EV induces cyst formation and anovulation in rodents.

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.

Keywords

References

  1. Andersson S: The functional background in acupuncture effects. Scand J Rehabil Med Suppl 29 : 31-60, 1993
  2. Bai YH, Lim SC, Song CH, Bae CS, Jin CS, Choi BC, Jang CH, Lee SH, Pak SC: Electro-acupuncture reverses nerve growth factor abundance in experimental polycystic ovaries in the rat. Gynecol Obstet Invest 57(2) : 80-85, 2004 https://doi.org/10.1159/000075382
  3. Barria A, Leyton V, Ojeda SR, Lara HE: Ovarian steroidal response to gonadotropins and beta-adrenergic stimulation is enhanced in polycystic ovary syndrome: role of sympathetic innervation. Endocrinology 133(6) : 2696-2703, 1993 https://doi.org/10.1210/en.133.6.2696
  4. Brawer JR, Munoz M, Farookhi R: Development of the polycystic ovarian condition (PCO) in the estradiol valerate-treated rat. Biol Reprod 35(3) : 647-655, 1986 https://doi.org/10.1095/biolreprod35.3.647
  5. Chen BY: Acupuncture normalizes dysfunction of hypothalamicpituitary-povarian axis. Acupunct Electrother Res 22(2) : 97-108, 1997 https://doi.org/10.3727/036012997816356734
  6. Christensen LP: Ginsenosides chemistry, biosynthesis, analysis, and potential health effects. Adv Food Nutr Res 55 : 1-99, 2009 https://doi.org/10.1016/S1043-4526(08)00401-4
  7. Dissen GA, Hill DF, Costa ME, Les Dees CW, Lara HE, Ojeda SR:A role for trkA nerve growth factor receptors in mammalian ovulation. Endocrinology 137(1) : 198-209, 1996 https://doi.org/10.1210/en.137.1.198
  8. Franks S: Polycystic ovary syndrome. N Engl J Med 333 : 853-861, 1995 https://doi.org/10.1056/NEJM199509283331307
  9. Garcia-Rudaz C, Armando I, Levin G, Escobar ME, Barontini M:Peripheral catecholamine alterations in adolescents with polycystic ovary syndrome. Clin Endocrinol 49(2) : 221-228, 1998 https://doi.org/10.1046/j.1365-2265.1998.00511.x
  10. Heider U, Pedal I, Spanel-Borowski K: Increase in nerve fibers and loss of mast cells in polycystic and postmenopausal ovaries. Fertil Steril 75(6) : 1141-1147, 2001 https://doi.org/10.1016/S0015-0282(01)01805-2
  11. Kim HS, Lee JH, Goo YS, Nah SY: Effects of ginsenosides on $Ca^{2+}$ channels and membrane capacitance in rat adrenal chromaffin cells. Brain Res Bull 46(3) : 245-251, 1998 https://doi.org/10.1016/S0361-9230(98)00014-8
  12. Kousta E, White DM, Franks S: Modern use of clomiphene citrate in induction of ovulation. Hum Reprod Update 3(4) : 359-365, 1997 https://doi.org/10.1093/humupd/3.4.359
  13. Lara HE, Dissen GA, Leyton V, Paredes A, Fuenzalida H, Fiedler JL, Ojeda SR: An increased intraovarian synthesis of nerve growth factor and its low affinity receptor is a principal component of steroid-induced polycystic ovary in the rat. Endocrinology 141(3) : 1059-1072, 2000 https://doi.org/10.1210/en.141.3.1059
  14. Lara HE, Ferruz JL, Luza S, Bustamante DA, Borges Y, Ojeda SR:Activation of ovarian sympathetic nerves in polycystic ovary syndrome. Endocrinology 133(6) : 2690-2695, 1993 https://doi.org/10.1210/en.133.6.2690
  15. Lee JC, Pak SC, Lee SH, Lim SC, Bai YH, Jin CS, Kim JS, Na CS, Bae CS, Oh KS, Choi BC: The effect of herbal medicine on nerve growth factor in estradiol valerate-induced polycystic ovaries in rats. Am J Chin Med 31(6) : 885-895, 2003 https://doi.org/10.1142/S0192415X03001636
  16. Levi-Montalcini R: The nerve growth factor 35 years later. Science 237(4819) : 1154-1162, 1987 https://doi.org/10.1126/science.3306916
  17. Lobo RA: The role of neurotransmitters and opioids in polycystic ovarian syndrome. Endocrinol Metab Clin North Am 17(4) : 667-683, 1988
  18. Lobos E, Gebhardt C, Kluge A, Spanel-Borowski K: Expression of nerve growth factor (NGF) isoforms in the rat uterus during pregnancy:accumulation of precursor proNGF. Endocrinology 146(4) : 1922-1929, 2005 https://doi.org/10.1210/en.2004-0925
  19. Manni L, Holmang A, Lundeberg T, Aloe L, Stener-Victorin E: Ovarian expression of alpha (1)- and beta (2)-adrenoceptors and p75 neurotrophin receptors in rats with steroid-induced polycystic ovaries. Auton Neurosci 118(1-2) : 79-87, 2005 https://doi.org/10.1016/j.autneu.2005.01.004
  20. Pak SC, Lim SC, Nah SY, Lee JA, Hill JA, Bae CS: Role of Korean red ginseng total saponins in rat infertility induced by polycystic varies. Fertil steril 4 Suppl(2) : 139-4311, 2005
  21. Paradisi R, Grossi G, Venturoli S, Capelli M, Porcu E, Fabbri R, Pasquali R, Flamigni C: Evidence for a hypothalamic alteration of catecholamine metabolism in polycystic ovary syndrome. Clin Endocrinol 29(3) : 317-326, 1988 https://doi.org/10.1111/j.1365-2265.1988.tb01230.x
  22. Parra C, Fiedler JL, Luna SL, Greiner M, Padmanabhan V, Lara HE: Participation of vasoactive intestinal polypeptide in ovarian steroids production during the rat estrous cycle and in the development of estradiol valerate-induced polycystic ovary. Reproduction 133(1) : 147-154, 2007 https://doi.org/10.1530/rep.1.01214
  23. Stener-Victorin E, Lundeberg T, Cajander S, Aloe L, Manni L, Waldenström U, Janson PO: Steroid-induced polycystic ovaries in rats: effect of electro-acupuncture on concentrations of endothelin-1 and nerve growth factor (NGF), and expression of NGF mRNA in the ovaries, the adrenal glands, and the central nervous system. Reprod Biol Endocrinol 1 : 33, 2003 https://doi.org/10.1186/1477-7827-1-33
  24. Stener-Victorin E, Lundeberg T, Waldenstrom U, Bileviciute-Ljungar I, Janson PO: Effects of electro-acupuncture on corticotropinreleasing factor in rats with experimentally-induced polycystic ovaries. Neuropeptides 35(5-6) : 227-231, 2001 https://doi.org/10.1054/npep.2002.0878
  25. Stener-Victorin E, Lundeberg T, Waldenström U, Manni L, Aloe L, Gunnarsson S, Janson PO: Effects of electro-acupuncture on nerve growth factor and ovarian morphology in rats with experimentally induced polycystic ovaries. Biol Reprod 63(5) : 1497-1503, 2000 https://doi.org/10.1095/biolreprod63.5.1497
  26. Stener-Victorin E, Waldenstr$\ddot{o}$m U, T$\ddot{a}$gnfors U, Lundeberg T, Lindstedt G, Janson PO: Effects of electro-acupuncture on anovulation in women with polycystic ovary syndrome. Acta Obstet Gynecol Scand 79(3) : 180-188, 2000 https://doi.org/10.1080/j.1600-0412.2000.079003180.x