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Leptin upregulates β3-integrin expression and interleukin-1β upregulates leptin and leptin receptor expression in human endometrial epithelial cell cultures

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Abstract

Human endometrium and endometrial epithelial cells (EECs) either cultured alone or cocultured with human embryos express leptin and leptin receptor. This study compares the effect of leptin with that of interleukin-1β (IL-1β) on the expression of β3-EEC integrin, a marker of endometrial receptivity. Both cytokines increased the expression of β3-EEC at concentrations in the range of 0.06–3 nM; however, leptin exhibited a significantly greater effect than IL-1β. We also determined the regulatory effects of IL-1β on leptin secretion and on the expression of leptin and leptin receptor at the protein level in both EEC and endometrial stromal cell (ESC) cultures. In EEC cultures, IL-1β upregulated secretion of leptin and expression of both leptin and leptin receptors. No effect of IL-1β was found in the ESC cultures. However, leptin exhibited marginal upregulation of leptin receptor. The upregulation of β3-integrin and leptin/leptin receptor expression by IL-1β in EEC cultures indicates that both cytokines may be implicated in embryonic-maternal cross-talk during the early phase of human implantation. Our present data also raise the possibility that leptin is an endometrial molecular effector of IL-1β action on β3-integrin upregulation. Thus, a new role for leptin in human reproduction as an autocrine/paracrine regulator of endometrial receptivity is proposed.

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References

  1. Tabibzadeh, S. S. (1991). Endocr. Rev. 12, 272–290.

    PubMed  CAS  Google Scholar 

  2. De los Santos, M. J., Mercader, A., Frances, A., Portoles, E., Remohi, J., Pellicer, A., and Simón, C. (1996). Biol. Reprod. 54, 563–574.

    Article  PubMed  Google Scholar 

  3. Russel, J. S., Simón, C., Rubio, M. C., Pape, A. R., Wen, Y., Huang, H.-Y., Bielfeld, P., and Polan, M. L. (1998). Hum. Reprod. 3, 2206–2211.

    Article  Google Scholar 

  4. Paula-Lopes, F. F., de Moraes, A. A., Edwards, J. L., Justice, J. E., and Hansen, P. J. (1998). Biol. Reprod. 59, 1406–1412.

    Article  PubMed  CAS  Google Scholar 

  5. Sheth, K. V., Rovca, G. L., Al-Sedairy, S. T., Parher, R. S., Hamilton, C. J. C. M., and Al-Abdul Jabbar, F. (1991). Fertil. Steril. 55, 952–957.

    PubMed  CAS  Google Scholar 

  6. Simón, C., Piquette, G. N., Frances, A., and Polan, M. L. (1993). J. Clin. Endocrinol. Metab. 77, 549–555.

    Article  PubMed  Google Scholar 

  7. Simón, C., Frances, A., Piquette, G., Hendriclson, M., Milki, A., and Polan, M. L. (1994). J. Clin. Endocrinol. Metab. 78, 847–854.

    Article  PubMed  Google Scholar 

  8. Simón, C., Frances, A., Piquette, G. N., el Danasouri, I., Zurawski, G., Dang, W., and Polan, M. L. (1994). Endocrinology 134, 521–528.

    Article  PubMed  Google Scholar 

  9. Simón, C., Valbuena, D., Krussel, J., Bernal, A., Murphy, C. R., Shaw, T., Pellicer, A., and Polan, M. L. (1998). Fertil. Steril. 70, 896–906.

    Article  PubMed  Google Scholar 

  10. Illera, M. J., Cullinan, E., Gui, Y., Yuan, L., Beyler, S. A., and Lessey, B. A. (2000). Biol. Reprod. 62, 1285–1290.

    Article  PubMed  CAS  Google Scholar 

  11. Lessey, B. A., Damjanovich, L., Coutifarís, C., Castelbaum, A., Albelda, S. M., and Buck, C. A. (1992). J. Clin. Invest. 90, 188–195.

    PubMed  CAS  Google Scholar 

  12. Lessey, B. A. (1994). Fertil. Steril. 61, 812–814.

    PubMed  CAS  Google Scholar 

  13. Lessey, B. A., Castelbaum, A. J., Sawin, S. J., and Sun, J. (1995). Fertil. Steril. 63, 535–542.

    PubMed  CAS  Google Scholar 

  14. Gonzalez, R. R., Palomino, A., Boric, A., Vega, M., and Devoto, L. (1999). Hum. Reprod. 4, 2485–2492.

    Article  Google Scholar 

  15. Lessey, B. A. and Castelbaum, A. J. (1995). Br. J. Obstet. Gynaecol. 102, 347–348.

    PubMed  CAS  Google Scholar 

  16. Meyer, W. R., Castelbaum, A. J., Somkuti, S., Sagoskin, A. W., Doyle, M., Harris, J. E., and Lessey, B. A. (1997). Hum. Reprod. 12, 1393–1398.

    Article  PubMed  CAS  Google Scholar 

  17. Gonzalez, R. R., Palomino, A., Vantman, D., Gabler, F., and Devoto, L. (2001). Early Preg. Biol. Med. 5, 132–143.

    CAS  Google Scholar 

  18. Gonzalez, R. R., Simón, C., Caballero-Campo, P., Norman, R., Chardonnens, D., Devoto, L., and Bischof, P. (2000). Hum. Reprod. Update 6, 290–300.

    Article  PubMed  CAS  Google Scholar 

  19. Fantuzzi, G. and Faggioni, R. (2000). J. Leuk. Biol. 68, 437–446.

    CAS  Google Scholar 

  20. Sierra-Honigmann, M. R., Nath, A. K., Murakami, C., Garcia-Cardena, G., Papetropoulos, A., Sessa, W. C., Madge, L. A., Schechner, J. S., Schwabb, M. B., Polverini, P. J., and Flores-Riveros, J. R. (1998). Science 282, 1683–1686.

    Article  Google Scholar 

  21. Karlsson, C., Lindell, K., Svensson, E., Bergh, C., Lind, P., Billig, H., Carlsson, L. M., and Carlsson, B. (1997). J. Clin. Endocrinol. Metab. 82, 4144–4148.

    Article  PubMed  CAS  Google Scholar 

  22. Cioffi, J. A., Van Blerkom, J., Antczak, M., Shafer, A., Wittmer, S., and Snodgrass, H. R. (1997). Mol. Hum. Reprod. 3, 467–472.

    Article  PubMed  CAS  Google Scholar 

  23. Antczak, M. and Van Blerkom, J. (1997). Mol. Hum. Reprod. 3, 1067–1086.

    Article  PubMed  CAS  Google Scholar 

  24. Kitawaki, J., Koshiba, H., Ishihara, H., Kusuki, I., Tsukamoto, K., and Honjo, H. (2000). J. Clin. Endocrinol. Metab. 85, 1946–1950.

    Article  PubMed  CAS  Google Scholar 

  25. Alfer, J., Muller-Schottle, F., Classen-Linke, I., von Rango, U., Happel, L., Beier-Hellwig, K., Rath, W., and Beier, H. M. (2000). Mol. Hum. Reprod. 6, 595–601.

    Article  PubMed  CAS  Google Scholar 

  26. Gonzalez, R. R., Caballero-Campo, P., Jasper, M., Mercader, A., Devoto, L., Pellicer, A., and Simón, C. (2000). J. Clin. Endocrinol. Metab. 85, 4883–4888.

    Article  PubMed  CAS  Google Scholar 

  27. Masuzaki, H., Ogawa, Y., Sagawa, N., Hosoda, K., Matsumoto, T., Hiroko, M., Nishimura, M., Yoshimasa, Y., Tanaka, I., Mori, T., and Nakao, K. (1997). Nat. Med. 3, 1029–1033.

    Article  PubMed  CAS  Google Scholar 

  28. Senaris, R., Garcia-Caballero, T., Casabiell, X., Gallego, R., Castro, R., Considine, R. V., and Casanueva, F. F. (1997). Endocrinology 138, 4501–4504.

    Article  PubMed  CAS  Google Scholar 

  29. Tena-Sempere, M., Pinilla, L., Zhang, F. P., Gonzalez, L. C., Huhtaniemi, I., Casanueva, F. F., Dieguez, C., and Aguilar, E. (2001). Biol. Reprod. 64, 634–643.

    Article  PubMed  CAS  Google Scholar 

  30. Baumann, H., Morella, K. K., White, D. W., Dembski, M., Bailon, P. S., Kim, H., Lai, C. F., and Tartaglia, L. A. (1996). Proc. Natl. Acad. Sci. USA 93, 8374–8378.

    Article  PubMed  CAS  Google Scholar 

  31. Campfield, L. A., Smith, F. J., and Burn, P. (1996). Horm. Metab. Res. 28, 619–632.

    Article  PubMed  CAS  Google Scholar 

  32. Wang, Y., Kuropatwinski, K. K., White, D. W., Hawley, T. S., Hawley, R. G., Tartaglia, L. A., and Baumann, H. (1997). J. Biol. Chem. 272, 16,216–16,223.

    CAS  Google Scholar 

  33. Chehab, F., Lom, M., and Lu, R. (1996). Nat. Genet. 12, 318–320.

    Article  PubMed  CAS  Google Scholar 

  34. Mounzih, K., Lu, R., and Chehab, F. F. (1997). Endocrinology 138, 1190–1193.

    Article  PubMed  CAS  Google Scholar 

  35. Grunfeld, C., Zhao, C., Fuller, J., Pollack, A., Moser, A., Friedman, J., and Feinggold, K. R. (1966). J. Clin. Invest. 97, 2152–2157.

    Article  Google Scholar 

  36. Sarraf, P., Frederich, R. C., Turner, E. M., Ma, G., Jaskowiak, N. T., Rivet, D. J. III, Flier, J. S., Lowell, B. B., Fraker, D. L., and Alexander, H. R. (1997). J. Exp. Med. 185, 171–175.

    Article  PubMed  CAS  Google Scholar 

  37. Janik, J. E., Curti, B. D., Considine, R. V., Rager, H. C., Powers, G. C., Alvord, W. G., Smith, J. W. II, Gause, B. L., and Kopp, W. C. (1997). J. Clin. Endocrinol. Metab. 82, 3084–3086.

    Article  PubMed  CAS  Google Scholar 

  38. Faggioni, R., Fantuzzi, G., Fuller, J., Dinarello, C. A., Feingold, K. R., and Grunfeld, C. (1998). Am. J. Physiol. 274(1)(Pt. 2), R204-R208.

    PubMed  CAS  Google Scholar 

  39. Chardonnens, D., Cameo, P., Aubert, M. L., Pralong, F. P., Islami, D., Campana, A., Gaillard, R. C., and Bischof, P. (1999). Mol. Hum. Reprod. 5, 1077–1082.

    Article  PubMed  CAS  Google Scholar 

  40. Meisser, A., Cameo, P., Islami, D., Campana, A., and Bischof, P. (1999). Mol. Hum. Reprod. 5, 1055–1058.

    Article  PubMed  CAS  Google Scholar 

  41. Castelluci, M., De Matteis, R., Meisser, A., Canullo, R., Monsurro, V., Islami, D., Sarzani, R., Marzioni, D., Cinti, S., and Bischof, P. (2000). Mol. Hum. Reprod. 6, 951–958.

    Article  Google Scholar 

  42. Gonzalez, R. R., Devoto, L., Campana, B., and Bischof, P. (2001). Endocrine, in press.

  43. Mounzih, K., Qiu, J., Wwart-Toland, A., and Chehab, F. (1998). Endocrinology 139, 5259–5262.

    Article  PubMed  CAS  Google Scholar 

  44. Simon, C., Moreno, C., Remohi, J., and Pellicer, A. J. (1998). J. Reprod. Immunol. 39, 117–131.

    Article  PubMed  CAS  Google Scholar 

  45. Simon, C., Gimeno, M. J., Mercader, A., O’Connor, J. E., Remohi, J., Polan, M. L., and Pellicer, A. (1997). J. Clin. Endocrinol. Metab. 82, 2607–2616.

    Article  PubMed  CAS  Google Scholar 

  46. Tabibzadeh, S. and Sun, X. Z. (1992). Hum. Reprod. 7, 1214–1221.

    PubMed  CAS  Google Scholar 

  47. Sahakian, V., Anners, J., Haskill, S., and Halme, J. (1993). Fertil. Steril. 60, 276–279.

    PubMed  CAS  Google Scholar 

  48. Simon, C., Frances, A., Lee, B. Y., Mercader, A., Huynh, T., Remohi, J., Polan, M. L., and Pellicer, A. (1995). Hum. Reprod. 10, 2472–2477.

    PubMed  CAS  Google Scholar 

  49. Tanaka, T., Sakamoto, T., Mizuno, K., Umesaki, N., and Ogita, S. (2000). Horm. Res. 53, 300–304.

    Article  PubMed  CAS  Google Scholar 

  50. Huang, H. Y., Wen, Y., Kruessel, J. S., Raga, F., Soong, Y. K., and Polan, M. L. (2001). J. Clin. Endocrinol. Metab. 86, 1387–1393.

    Article  PubMed  CAS  Google Scholar 

  51. Simon, C., Piquette, G. N., Frances, A., el-Danasouri, I., Irwin, J. C., and Polan, M. L. (1994). J. Clin. Endocrinol. Metab. 78, 675–682.

    Article  PubMed  CAS  Google Scholar 

  52. Gabay, C., Dreyer, M. G., Pellegrinelli, N., Chicheportiche, R., and Meier, C. A. (2001). J. Clin. Endocrinol. Metab. 86, 783–791.

    Article  PubMed  CAS  Google Scholar 

  53. Hosoi, T., Okuma, Y., and Nomura, Y. (2000). Biochem. Biophys. Res. Commun. 273, 312–315.

    Article  PubMed  CAS  Google Scholar 

  54. Loffreda, S., Yang, S. Q., Lin, H. Z., Karp, C. L., Brengman, M. L., Wang, D. J., Klein, A. S., Bulkley, G. B., Bao, C., Noble, P. W., Lane, M. D., and Diehl, A. M. (1998). FASEB J. 12, 57–65.

    PubMed  CAS  Google Scholar 

  55. Satyaswaroop, P. G., Bressler, R. S., de la Pena, M. M., and Gurpide, E. (1979). J. Clin. Endocrinol. Metab. 48, 639–641.

    Article  PubMed  CAS  Google Scholar 

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  1. Boston Biomedical Research Institute, 64 Grove Street, 02472, Watertown, MA

    Ruben Rene Gonzalez & Paul Leavis

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Correspondence to Ruben Rene Gonzalez.

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Gonzalez, R.R., Leavis, P. Leptin upregulates β3-integrin expression and interleukin-1β upregulates leptin and leptin receptor expression in human endometrial epithelial cell cultures. Endocr 16, 21–28 (2001). https://doi.org/10.1385/ENDO:16:1:21

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  • DOI: https://doi.org/10.1385/ENDO:16:1:21

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