Clinical and Experimental Reproductive Medicine

The Korean Society for Reproductive Medicine (대한생식의학회)
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Transforming Growth Factor-$\beta$ is a Possible Paracrine Mediator in the Human Endometrial Decidualization

인간자궁내막의 탈락막화 (Decudualization)에 있어서 TGF-$\beta$ (Transforming Growth Factor-$\beta$)의 역할

  • Park, Dong-Wook (Department Molecular Science and Technology, Ajou University) ;
  • Choi, Dong-Soon (Department Molecular Science and Technology, Ajou University) ;
  • Kim, Mi-Ran (Department of Obstetrics and Gynecology, School of Medicine, Ajou University) ;
  • Hwang, Kyung-Joo (Department of Obstetrics and Gynecology, School of Medicine, Ajou University) ;
  • Jo, Mi-Yeong (Department of Obstetrics and Gynecology, School of Medicine, Ajou University) ;
  • Ahn, Seong-Hee (Department of Obstetrics and Gynecology, School of Medicine, Ajou University) ;
  • Min, Churl-K. (Department of Biological Science, Ajou University) ;
  • Ryu, Hee-Sug (Department of Obstetrics and Gynecology, School of Medicine, Ajou University)
  • 박동욱 (아주대학교 대학원 분자과학기술학과) ;
  • 최동순 (아주대학교 대학원 분자과학기술학과) ;
  • 김미란 (아주대학교 의과대학 산부인과학교실) ;
  • 황경주 (아주대학교 의과대학 산부인과학교실) ;
  • 조미영 (아주대학교 의과대학 산부인과학교실) ;
  • 안성희 (아주대학교 의과대학 산부인과학교실) ;
  • 민철기 (아주대학교 자연대학 생명과학과) ;
  • 유희석 (아주대학교 의과대학 산부인과학교실)
  • Published : 2003.03.30
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Abstract

Objectives: To investigate the role of TGF (Transforming growth factor-$\beta$) involved in the paracrinic communication during decidualization between UEC (uterine epithelial cells) and USC (uterine stromal cells), we have employed a co-culture system composed of human endometrial epithelial and stromal cells in defined hormonal conditions. Design: In the co-culture, endometrial epithelial cells cultured in the matrigel-coated cell culture insert are seeded on top of the endometrial stromal cells cultured within a collagen gel. The co-culture was maintained for 48 hours under the following hormonal conditions: progesterone dominant condition (100 nM P4 and 1 nM E2) or estrogen-dominant condition (100 nM E2 and 1 nM P4). 10 ng/ ml HGF and/or 10 ng/ml TGF-$\beta$1 are added. Methods: RT-PCR is utilized to detect mRNAs quantitatively. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining are utilized to detect proteins in the tissue. Results: Prolactin mRNA is expressed in the co-cultured stromal cells under the progesterone dominant condition. TGF-$\beta$1 and its receptors are expressed in both the co-cultured epithelial and stromal cells irrespective of the steroid present, which is in contrast with no or negligible expression of TGF-$\beta$1 or its receptor in cells separately cultured. Both estrogen and progesterone significantly elevate the concentration of hepatocyte growth factor (HGF) in the conditioned medium of the co-culture with the value of 4, 325 pg/ml in E2-dominant and 2, 000 pg/ml in P4-dominant condition compare to 150 pg/ml in no hormone. In separately cultured stromal cells, administration of HGF induces the expression of TGF receptor 1 in both hormonal conditions, but induction of TGF receptor 2 is only manifest in the P4-dominant condition. Administration of TGF-$\beta$ and HGF directly induce the decidualization marker prolactin mRNA in separately cultured stromal cells. Conclusion: It is likely that steroid hormones induces prolactin mRNA indirectly by promoting the cell to cell communication between the stromal and the epithelial cells. TGF-$\beta$ and HGF are two possible paracrine mediators in the human endometrial decidualization.

Keywords

References

  1. Noyes RW, Hertig AT, Rock J. Dating of endometrial biopsy. Fertil Steril 1950; 1: 3-25 https://doi.org/10.1016/S0015-0282(16)30062-0
  2. Tang B, Guller S, Gurpid E. Cyclic adenosine 3' 5'-monophosphate induces prolactin expression in stromal cells isolated from human proliferative endometrium. Endocrinology 1993; 133: 2197-203 https://doi.org/10.1210/en.133.5.2197
  3. Tang B, Grupide E. Direct effect of gonodotropins on decidualization of human endometrial stromal cells. J Steroid Biochem Mol Biol 1993; 47: 115-21 https://doi.org/10.1016/0960-0760(93)90064-4
  4. Frank GR, Brar AK, Cedars MI, Handwerger S. Prostaglandin E2 enhances human endometrial cell differentiation. Endocrinology 1994; 134: 258-63 https://doi.org/10.1210/en.134.1.258
  5. Moses HL, Coffey RJ Jr, Leof EB, Lyons RM, Keski-Oja J. Transforming growth factor beta regulation of cell proliferation. J Cell Physiol Suppl 1987; 5: 1-7
  6. Moses HL, Serra R. Regulation of differentiation by TGF-beta. Curr Opin Genet Dev 1996; 6: 581-6 https://doi.org/10.1016/S0959-437X(96)80087-6
  7. Herrmann M, Scholmerich J, Straub RH. Influence of cytokines and growth factors on distinct steroidogenic enzymes in vitro: a short tabular data collection. Ann N Y Acad Sci 2002; 966: 166-86 https://doi.org/10.1111/j.1749-6632.2002.tb04213.x
  8. Renner U, Lohrer P, Schaaf L, Feirer M, Schmitt K, Onofri C, et al. Transforming growth factor-beta stimulates vascular endothelial growth factor production by folliculostellate pituitary cells. Endocrinology 2002; 143: 3759-65 https://doi.org/10.1210/en.2002-220283
  9. Akhurst RJ, Derynck R. TGF-beta signaling in cancer-a double-edged sword. Trends Cell Biol 2001; 11: s44-51
  10. Casslén B, Sandberg T, Gustavsson B, Willén R, Nilbert M. Transforming growth factor beta1 in the human endometrium. Cyclic variation, increased expression by estradiol and progesterone, and regulation of plasminogen activators and plasminogen activator inhibitor-1. Biol Reprod 1998; 58: 1343-50 https://doi.org/10.1095/biolreprod58.6.1343
  11. Bruner KL, Eisenberg E, Gorstein F, Osteen KG. Progesterone and transforming growth factor-beta coordinately regulate suppression of endometrial matrix metalloproteinases in a model of experimental endomeriosis. Steroid 1999; 64: 648-53 https://doi.org/10.1016/S0039-128X(99)00048-3
  12. Bruner KL, Roders WH, Gold LI, Korc M, Hargrove JT, Matrisian LM, et al. Transforming growth factor beta mediates the progesterone suppression on an epithelial metalloproteinase by adjacent stroma in the human endometrium. Proc. Natl Acad Sci USA 1995; 92: 7362-6 https://doi.org/10.1073/pnas.92.16.7362
  13. Odekone S, Matt D, Strom S, Rifkin DB. Requirement for receptor-bound urokinase in plasmindependent cellular conversion of latent TGF-beta to TGF-beta. J Cell Physiol 1994; 158: 398-407 https://doi.org/10.1002/jcp.1041580303
  14. Rotraud W. The transforming growth factor-beta signaling pathway in tumorigenesis. Current Opinion in Oncology 2001; 13: 70-7 https://doi.org/10.1097/00001622-200101000-00014
  15. Ando N, Hirahara F, Fukushima J, Kawamoto S, Okuda K, Funabashi T, et al. Differential gene expression of TGF-beta isoforms and TGF-beta receptors during the first timester of pregnancy at the human maternal-fetal interface. Am J Reprod Immunol 1998; 40: 48-56 https://doi.org/10.1111/j.1600-0897.1998.tb00388.x
  16. Nakamura T, Nishizawa T, Hagiya M, Seki T, Shimonishi M, Sugimura A, et al. Molecular cloning and expression of human hepatocyte growth factor. Nature 1989; 42: 440-3
  17. Sugawara J, Fukaya T, Murakami T, Yoshida H, Yajima A. Hepatocyte growth factor stimulated proliferation, migration, and lumen formation of human endometrial epithelial cells in vitro. Biol Reprod 1997; 57: 936-42 https://doi.org/10.1095/biolreprod57.4.936
  18. Kauma SW, Bae-Jump V, Walsh SW. Hepatocyte growth factor stimulates trophoblast invasion: A potential mechanism for abnormal placentation in preeclampsia. J Clin Endocrin Metab 1999; 84:4092-6 https://doi.org/10.1210/jc.84.11.4092
  19. Negami AI, Sasaki H, Kawakami Y, Kamitani N, Kotsuji F, Tominaga T, Nakamura T. Serum human hepatocyte growth factor in human menstrual cycle and pregnancy: a novel serum marker on regeneration and reconstruction of human endometrium. Horm Res 1995; 44 suppl 2: 42-6
  20. Irwin JC, Kirk D, King RJB, Quigley MM, Gwatkin RBL. Hormonal regulation of human endometrial stromal cells in culture: an in vivo model for decidualization. Fertil Steril 1989; 52: 761-8 https://doi.org/10.1016/S0015-0282(16)61028-2
  21. Hearn JP. The embryo-maternal dialogue during early pregnancy in primates. J Reprod Fertil 1986; 76: 809-19 https://doi.org/10.1530/jrf.0.0760809
  22. Bentin-Ley U, Pedersen B, Lindenberg S. Isolation and culture of human endometrial cells in a threedimensional culture system. J Reprod Fertil 1994; 101: 327-32 https://doi.org/10.1530/jrf.0.1010327
  23. Wegner CC, Carson DD. Mouse uterine stromal cells secrete a 30 kilodalton protein in response to coculture with uterine epithelial cells. Endocrinology 1992; 131: 2565-72 https://doi.org/10.1210/en.131.6.2565
  24. Lessey BA, Castelbaum AJ, Wolf L, Greene W, Paulson M, Meyer WR, et al. Use of integrins to date the endometrium. Fertil Steril 2000; 73: 779-87 https://doi.org/10.1016/S0015-0282(99)00604-4
  25. Telgmann R, Gellersen B. Marker genes of decidulization: activation of the decidual prolactin gene. Hum Reprod Update 1998; 4: 472-9 https://doi.org/10.1093/humupd/4.5.472
  26. Makrigiannakis A, Margioris AN, Chatzaki E, Zoumakis E, Chrousos GP, Gravanis A. The decidualizing effect of progesterone may involve direct transcriptional activation of corticotrophin-releasing hormone from human endometrial stromal cells. Mol Hum Reprod 1999; 5: 789-96 https://doi.org/10.1093/molehr/5.9.789