Immunohistochemical Study on the Effect of Dexamethasone on the Luteolysis of Corpus Luteum of the Rat

Dexamethasone이 황체용해에 미치는 영향에 관한 면역조직화학적 연구

  • Park, Sun-Hee (Department of Obstetrics and Gynecology, College of Medicine, Chungnam National University) ;
  • Ko, Young-Bok (Department of Obstetrics and Gynecology, College of Medicine, Chungnam National University) ;
  • Rhee, Yun-Ee (Department of Obstetrics and Gynecology, College of Medicine, Chungnam National University) ;
  • Noh, Heung-Tae (Department of Obstetrics and Gynecology, College of Medicine, Chungnam National University) ;
  • Kim, Won-Sik (Depatment of Anatomy, College of Medicine, Chungnam National University)
  • 박선희 (충남대학교 의과대학 산부인과학교실) ;
  • 고영복 (충남대학교 의과대학 산부인과학교실) ;
  • 이윤이 (충남대학교 의과대학 산부인과학교실) ;
  • 노흥태 (충남대학교 의과대학 산부인과학교실) ;
  • 김원식 (충남대학교 의과대학 해부학교실)
  • Published : 2008.03.30

Abstract

Objective: This study was attempted to look at the effect of dexamethasone on the luteolysis of corpus luteum in rats by immunohistochemical study. Methods: Counting with an optical microscope was conducted to make a comparison on difference in luteolysis and penetration of macrophage into three groups: control group of 30 female rats at 8 weeks of age, dexamethasone 0.1 mg administered group, and dexamethasone 1mg administered group. Results: As a result of TUNEL immunostaining, the percentage of luteolysis was significantly reduced in both dexamethasone 0.1 mg administered group and 1 mg administered group, and after ED1 immunostaining, macrophage invasion was reduced in dexamethasone 1 mg administered group. As a consequence of ED1 immunostaining, the immune response of macrophage was much decreased in dexamethasone 1 mg administered group than control group. Conclusion: Dexamethasone works on luteal cell, so it can suppress apoptosis. It can suppress luteolysis by suppression macrophage invasion into corpus luteum or suppress macrophage activation in corpus luteum.

목 적: Glucocorticoid가 황체용해에 미치는 효과의 기전의 일부를 면역 조직학적 연구를 통해 알아보고자 하였다. 연구방법: 8주령의 Rat 암컷 30마리 대조군, 덱사메타손 0.1 mg 투여군 및 덱사메타손 1mg 투여군의 3군으로 나누어 황체용해의 차이와 대식세포의 침투여부를 비교하기 위하여 광학현미경을 이용하여 계수하였다. 결 과: TUNEL 면역염색 결과 덱사메타손 0.1 mg 투여군과 1 mg 투여군 모두에서 대조군에 비해 황체용해의 비율이 현저히 감소하였고, ED1 면역염색 결과 덱사메타손 1 mg 투여군에서 대식세포의 황체 내 침투가 현저히 억제된 것으로 나타났다. ED1 면역염색 결과 덱사메타손 1 mg 투여군에서 대식세포의 면역반응성이 대조군에 비해 감소되어 나타났다. 결 론: 덱사메타손은 직접 황체세포에 작용하여 세포자멸사를 억제한다. 또한 대량 투여했을 때는 대식세포의 황체 내 침투를 억제하거나 황체 내에 이미 존재하는 대식세포의 활성화를 억제함으로써 황체용해를 억제한다.

Keywords

References

  1. Niswender GD, Nett TM. Corpus luteum and its control in infraprimate species. In: Knobil E, Neill JD(eds.), The Physiology of Reproduction. Vol 1, 2nd ed. New York: Raven Press; 1994: 781-816
  2. Okuda K, Sakumoto R. Multiple roles of TNF super family members in corpus luteum function. Reprod Biol Endocrinol 2003; 95-104 https://doi.org/10.1186/1477-7827-1-95
  3. Niswender GD, Juengel JL, Silva PJ, Rollyson MK, McIntush ER. Mechanisms controlling the function and life span of the corpus luteum. Physiol Rev 2000; 80: 1-29 https://doi.org/10.1152/physrev.2000.80.1.1
  4. Rothchild I. The regulation of the mammalian corpus luteum. Recent Prog Horm Res 1981; 37: 183-298
  5. Niswender GD, Juengel JL, McGuire WJ, Belfiore CJ, Wiltbank MC. Luteal function: The estrous cycle and early pregnancy. Biol Reprod 1994; 50: 239-47 https://doi.org/10.1095/biolreprod50.2.239
  6. Hehnke KE, Christenson LK, Ford SP, Taylor M. Macrophage infiltration into the porcine corpus luteum during prostaglandin F2${\alpha}$ induced luteolysis. Biol Reprod 1994; 50: 10-5 https://doi.org/10.1095/biolreprod50.1.10
  7. Parker CW. Neutrophil mechanisms. Am Rev Respir Dis 1991; 143: 59-60 https://doi.org/10.1164/ajrccm/143.3_Pt_2.S59
  8. Nothnick WB, Pate JL. Interleukin-1 beta is a potent stimulator of prostaglandin synthesis in bovine luteal cells. Biol Reprod 1990; 43: 898-903 https://doi.org/10.1095/biolreprod43.5.898
  9. De Greef WJ, van der Schoot P. Effects of dexamethasone on ovarian activity in rats. Acta Endocrinol (Copenh) 1987; 116: 350-6
  10. Sasson R, Amsterdam A. Stimulation of apoptosis in human granulosa cells from in vitro fertilization patients and its prevention by dexamethasone: involvement of cell contact and bcl-2 expression. J Clin Endocrinol Metab 2002; 87: 3441-51 https://doi.org/10.1210/jc.87.7.3441
  11. Amsterdam A, Sasson R. The anti-inflammatory action of glucocorticoids is mediated by cell type specific regulation of apoptosis. Mol Cell Endocrinol 2002; 189: 1-9 https://doi.org/10.1016/S0303-7207(01)00722-5
  12. Sawyer HR, Niswender KD, Braden TD, Niswender GD. Nuclear changes in ovine luteal cells in response to PGF2 alpha. Domest Anim. Endocrinol 1990; 7: 229-37 https://doi.org/10.1016/0739-7240(90)90029-Y
  13. Nett TM, McClellan MC, Niswender GD. Effects of prostaglandins on the ovine corpus luteum: blood flow, secretion of progesterone and morphology. Biol Reprod 1976; 15: 66-78 https://doi.org/10.1095/biolreprod15.1.66
  14. Azmi TI, O'Shea JD. Mechanism of deletion of endothelial cells during regression of the corpus luteum. Lab Invest 1984; 51: 206-17
  15. Duncan WC, Rodger FE, Illingworth PJ. The human corpus luteum: reduction in macrophages during simulated maternal recognition of pregnancy. Hum Reprod 1998; 13: 2435-42 https://doi.org/10.1093/humrep/13.9.2435
  16. Standaert FE, Zamora CS, Chew BP. Quantitative and qualitative changes in blood leukocytes in the porcine ovary. Am J Reprod Immunol 1991; 25: 163-8 https://doi.org/10.1111/j.1600-0897.1991.tb01088.x
  17. Gaytan F, Bellido C, Morales C, Sanchez-Criado JE. Both prolactin and progesterone are necessary for the induction of apoptosis in the regressing corpus luteum of the rat. Biol Reprod 1998; 59: 1200-6 https://doi.org/10.1095/biolreprod59.5.1200
  18. Bagavandoss P, Wiggins RC, Kunkel SL, Remick DG, Keyes PL. Tumor necrosis factor production and accumulation of inflammatory cells in the corpus luteum of pseudopregnancy and pregnancy in rabbits. Biol Reprod 1990; 42: 367-76 https://doi.org/10.1095/biolreprod42.2.367
  19. Hurwitz A, Dushnik M, Solomon H, Ben-Chetrit A, Finci- Yeheskel Z, Milwidsky A, et al. Cytokine-mediated regulation of rat ovarian function: interleukin-1 stimulates the accumulation of a 92-kilodalton gelatinase. Endocrinology 1993; 132: 2709-14 https://doi.org/10.1210/en.132.6.2709
  20. Hulboy DL, Rudolph LA, Matrisian LM. Matrix metalloproteinases as mediators of reproductive function. Mol Hum Reprod 1997; 3: 27-45 https://doi.org/10.1093/molehr/3.1.27
  21. Kraal G, Shiamatey-Koolma R, Hoffer M, Baker D, Scheper R. Histochemical identification of guinea-pig macrophages by monoclonal antibody MR-1. Immunology 1988; 65: 523-8
  22. Zolti M, Meirom R, Shemesh M, Wollach D, Mashiach S, Shore L, et al. Granulosa cells as a source and target organ for tumor necrosis factor-$\alpha$. FEBS Lett 1990; 261: 253-5 https://doi.org/10.1016/0014-5793(90)80565-Z
  23. Roby KF, Terranova PF. Localization of tumor necrosis factor (TNF) in the rat and bovine ovary using immunohistochemistry and cell blot: evidence for granulosa production. In: Hirshfield AN (ed.), Growth Factors and the Ovary. New York, Plenum Publishing Corporation 1989; 273-8
  24. Schreiber JR, Nakamura K, Erickson GF. Rat ovary glucocorticoid receptor: identification and characterization. Steroids 1982; 39: 569-84 https://doi.org/10.1016/0039-128X(82)90057-5
  25. Wen LP, Madani K, Fahrni JA, Duncan SR, Rosen GD. Dexamethasone inhibits lung epithelial cell apoptosis induced by IFN-gamma and Fas. Am J Physiol 1997; 273: 921-9
  26. Yamamoto M, Fukuda K, Miura N, Suzuki R, Kido T, Komatsu Y. Inhibition by dexamethasone of transforming growth factor beta1-induced apoptosis in rat hepatoma cells: a possible association with Bcl-xL induction. Hepatology 1998; 27: 959- 66 https://doi.org/10.1002/hep.510270410
  27. Messmer UK, Winkel G, Briner VA, Pfeilschifter J. Glucocorticoids potently block tumour necrosis factor-alpha- and lipopolysaccharide-induced apoptotic cell death in bovine glomerular endothelial cells upstream of caspase 3 activation. Br J Pharmacol 1999; 127: 1633-40 https://doi.org/10.1038/sj.bjp.0702726
  28. Messmer UK, Winkel G, Briner VA, Pfeilschifter J. Suppression of apoptosis by glucocorticoids in glomerular endothelial cells: effects on proapoptotic pathways. Br J Pharmacol 2000; 129: 1673-83 https://doi.org/10.1038/sj.bjp.0703255
  29. Kirsch TM, Friedman AC, Vogel RL, Flickinger GL. Macrophages in corpora lutea of mice: characterization and effects on steroid secretion. Biol Reprod 1981; 25: 629-38 https://doi.org/10.1095/biolreprod25.3.629