Fertility and Sterility
Volume 92, Issue 6 , Pages 1844-1849 , December 2009

Elevated ghrelin levels in the peritoneal fluid of patients with endometriosis: associations with vascular endothelial growth factor (VEGF) and inflammatory cytokines

  • Piotr Dziunycz, M.D.

      Affiliations

    • Department of Histology and Embryology, Center of Biostructure Research, Medical University of Warsaw, Warsaw, Poland
    • ,
  • Łukasz Milewski, M.D.

      Affiliations

    • Department of Histology and Embryology, Center of Biostructure Research, Medical University of Warsaw, Warsaw, Poland
    • ,
  • Dariusz Radomski, Ph.D.

      Affiliations

    • Division of Nuclear and Medical Electronics, Technical University of Warsaw, Warsaw, Poland
    • ,
  • Ewa Barcz, Ph.D.

      Affiliations

    • I Department of Obstetrics and Gynecology, Medical University of Warsaw, Warsaw, Poland
    • ,
  • Paweł Kamiński, Ph.D.

      Affiliations

    • I Department of Obstetrics and Gynecology, Medical University of Warsaw, Warsaw, Poland
    • ,
  • Piotr I. Roszkowski, Ph.D.

      Affiliations

    • II Department of Obstetrics and Gynecology, Medical University of Warsaw, Warsaw, Poland
    • ,
  • Jacek Malejczyk, Ph.D.

      Affiliations

    • Department of Histology and Embryology, Center of Biostructure Research, Medical University of Warsaw, Warsaw, Poland
    • Corresponding Author InformationReprint requests: J. Malejczyk, Department of Histology and Embryology, Center of Biostructure Research, Warsaw Medical University, Chałubińskiego 5, PL-02004 Warsaw, Poland (FAX: 48-22-629-52-82).

Received 2 June 2008 ,Revised 17 August 2008 ,Accepted 2 September 2008.

References 

  1. Giudice LC, Kao LC. Endometriosis. Lancet. 2004;364:1789–1799
  2. Gazvani R, Templeton A. New considerations for the pathogenesis of endometriosis. Int J Gynaecol Obstet. 2002;76:117–126
  3. Nisolle M, Donnez J. Peritoneal endometriosis, ovarian endometriosis, and adenomyotic nodules of the rectovaginal septum are three different entities. Fertil Steril. 1997;68:585–596
  4. Sampson JA. Peritoneal endometriosis due to menstrual dissemination of endometrial tissue into the peritoneal cavity. Am J Obst Gynecol. 1927;14:442–469
  5. Harada T, Iwabe T, Terakawa N. Role of cytokines in endometriosis. Fertil Steril. 2001;76:1–10
  6. Matarese G, De Placido G, Nikas Y, Alviggi C. Pathogenesis of endometriosis: natural immunity dysfunction or autoimmune disease?. Trends Mol Med. 2003;9:223–228
  7. Harada T, Kaponis A, Iwabe T, Taniguchi F, Makrydimas G, Sofikitis N, et al. Apoptosis in human endometrium and endometriosis. Hum Reprod Update. 2004;10:29–38
  8. McLaren J. Vascular endothelial growth factor and endometriotic angiogenesis. Hum Reprod Update. 2000;6:45–55
  9. Becker CM, D'Amato RJ. Angiogenesis and antiangiogenic therapy in endometriosis. Microvasc Res. 2007;74:121–130
  10. Dmowski WP. Immunological aspects of endometriosis. Int J Gynaecol Obstet. 1995;50(Suppl 1):3–10
  11. Ho HN, Wu MY, Yang YS. Peritoneal cellular immunity and endometriosis. Am J Reprod Immunol. 1997;38:400–412
  12. Nothnick WB. Treating endometriosis as an autoimmune disease. Fertil Steril. 2001;76:223–231
  13. Matarese G, Alviggi C, Sanna V, Howard JK, Lord GM, Carravetta C, et al. Increased leptin levels in serum and peritoneal fluid of patients with pelvic endometriosis. J Clin Endocrinol Metab. 2000;85:2483–2487
  14. De Placido G, Alviggi C, Carravetta C, Pisaturo ML, Sanna V, Wilding M, et al. The peritoneal fluid concentration of leptin is increased in women with peritoneal but not ovarian endometriosis. Hum Reprod. 2001;16:1251–1254
  15. Mahutte NG, Matalliotakis IM, Goumenou AG, Vassiliadis S, Koumantakis GE, Arici A. Inverse correlation between peritoneal fluid leptin concentrations and the extent of endometriosis. Hum Reprod. 2003;18:1205–1209
  16. La Cava A, Alviggi C, Matarese G. Unraveling the multiple roles of leptin in inflammation and autoimmunity. J Mol Med. 2004;82:4–11
  17. Budak E, Fernández Sánchez M, Bellver J, Cerveró A, Simón C, Pellicer A. Interactions of the hormones leptin, ghrelin, adiponectin, resistin, and PYY3-36 with the reproductive system. Fertil Steril. 2006;85:1563–1581
  18. Mitchell M, Armstrong DT, Robker RL, Norman RJ. Adipokines: implications for female fertility and obesity. Reproduction. 2005;130:583–597
  19. Kojima M, Kangawa K. Ghrelin: structure and function. Physiol Rev. 2005;85:495–522
  20. van der Lely AJ, Tschöp M, Heiman ML, Ghigo E. Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocr Rev. 2004;25:426–457
  21. Gnanapavan S, Kola B, Bustin SA, Morris DG, McGee P, Fairclough P, et al. The tissue distribution of the mRNA of ghrelin and subtypes of its receptor, GHS-R, in humans. J Clin Endocrinol Metab. 2002;87:2988–2991
  22. García MC, Lopez M, Alvarez CV, Casanueva F, Tena-Sempere M, Dieguez C. Role of ghrelin in reproduction. Reproduction. 2007;133:531–540
  23. Barreiro ML, Tena-Sempere M. Ghrelin and reproduction: a novel signal linking energy status and fertility?. Mol Cell Endocrinol. 2004;226:1–9
  24. Dixit VD, Schaffer EM, Pyle RS, Collins GD, Sakthivel SK, Palaniappan R, et al. Ghrelin inhibits leptin- and activation-induced proinflammatory cytokine expression by human monocytes and T cells. J Clin Invest. 2004;114:57–66
  25. Li WG, Gavrila D, Liu X, Wang L, Gunnlaugsson S, Stoll LL, et al. Ghrelin inhibits proinflammatory responses and nuclear factor-kappaB activation in human endothelial cells. Circulation. 2004;109:2221–2226
  26. Granado M, Priego T, Martín AI, Villanúa MA, López-Calderón A. Anti-inflammatory effect of the ghrelin agonist growth hormone-releasing peptide-2 (GHRP-2) in arthritic rats. Am J Physiol Endocrinol Metab. 2005;288:E486–E492
  27. American Fertility Society. Revised American Fertility Society classification of endometriosis. Fertil Steril. 1985;43:351–352
  28. Tanaka K, Minoura H, Isobe T, Yonaha H, Kawato H, Wang DF, et al. Ghrelin is involved in the decidualization of human endometrial stromal cells. J Clin Endocrinol Metab. 2003;88:2335–2340
  29. Tawadros N, Salamonsen LA, Dimitriadis E, Chen C. Facilitation of decidualization by locally produced ghrelin in the human endometrium. Mol Hum Reprod. 2007;13:483–489
  30. Breen EC. VEGF in biological control. J Cell Biochem. 2007;102:1358–1367
  31. Li A, Cheng G, Zhu GH, Tarnawski AS. Ghrelin stimulates angiogenesis in human microvascular endothelial cells: implications beyond GH release. Biochem Biophys Res Commun. 2007;353:238–243
  32. Konturek PC, Brzozowski T, Walter B, Burnat G, Hess T, Hahn EG, et al. Ghrelin-induced gastroprotection against ischemia-reperfusion injury involves an activation of sensory afferent nerves and hyperemia mediated by nitric oxide. Eur J Pharmacol. 2006;536:171–181
  33. Conconi MT, Nico B, Guidolin D, Baiguera S, Spinazzi R, Rebuffat P, et al. Ghrelin inhibits FGF-2-mediated angiogenesis in vitro and in vivo. Peptides. 2004;25:2179–2185
  34. Tropea A, Tiberi F, Minici F, Orlando M, Gangale MF, Romani F, et al. Ghrelin affects the release of luteolytic and luteotropic factors in human luteal cells. J Clin Endocrinol Metab. 2007;9:3239–3245
  35. Donnez J, Smoes P, Gillerot S, Casanas-Roux F, Nisolle M. Vascular endothelial growth factor (VEGF) in endometriosis. Hum Reprod. 1998;13:1686–1690
  36. Tan X-J, Lang J-H, Liu D-Y, Shen K, Leng J-H, Zhu L. Expression of vascular endothelial growth factor and thrombospondin-1 mRNA in patients with endometriosis. Fertil Steril. 2002;78:148–153
  37. Gilabert-Estellés J, Ramón LA, España F, Gilabert J, Vila V, Réganon E, et al. Expression of angigenic factors in endometriosis: relationship to fibrynolytic and metalloproteinase systems. Hum Reprod. 2007;2120–2127
  38. Khan KN, Masuzaki H, Fujishita A, Kitajima M, Sekine I, Ishimaru T. Higher activity by opaque endometriotic lesions than nonopaque lesions. Acta Obstet Gynecol Scand. 2004;83:375–382
  39. McLaren J, Prentice A, Charnock-Jones DS, Smith SK. Vascular endothelial growth factor (VEGF) concentrations are elevated in peritoneal fluid of women with endometriosis. Hum Reprod. 1996;11:220–223
  40. Kalu E, Sumar N, Giannopoulos T, Patel P, Croucher C, Sherriff E, et al. Cytokine profiles in serum and peritoneal fluid from infertile women with and without endometriosis. J Obstet Gynaecol Res. 2007;33:490–495
  41. Pupo-Noguieira A, de Oliveira RM, Petta CA, Podgaec S, Dias JA, Abrao MS. Vascular endothelial growth factor concentrations in the serum and peritoneal fluid of women with endometriosis. Int J Gynecol Obstet. 2007;99:33–37
  42. Mahnke JL, Dawood MY, Huang J-C. Vascular endothelial growth factor and interleukin-6 in peritoneal fluid of women with endometriosis. Fertil Steril. 2000;73:166–170
  43. Dembinski A, Warzecha Z, Ceranowicz P, Tomaszewska R, Stachura J, Konturek SJ, et al. Ghrelin attenuates the development of acute pancreatitis in rat. J Physiol Pharmacol. 2003;54:561–573
  44. Wu R, Dong W, Zhou M, Zhang F, Marini CP, Ravikumar TS, et al. Ghrelin attenuates sepsis-induced acute lung injury and mortality in rats. Am J Respir Crit Care Med. 2007;176:805–813
  45. Ataseven H, Bahcecioglu IH, Kuzu N, Yalniz M, Celebi S, Erensoy A, et al. The levels of ghrelin, leptin, TNF-alpha, and IL-6 in liver cirrhosis and hepatocellular carcinoma due to HBV and HDV infection. Mediators Inflamm. 2006;2006:78380
  46. Oral E, Olive DL, Arici A. The peritoneal environment in endometriosis. Hum Reprod Update. 1996;2:385–398
  47. Cheong YC, Shelton JB, Laird SM, Richmond M, Kudesia G, Li TC, et al. IL-1, IL-6 and TNF-α concentrations in the peritoneal fluid of women with pelvic adhesions. Hum Reprod. 2002;17:69–75
  48. Kawamura K, Sato N, Fukuda J, Kodama H, Kumagai J, Tanikawa H, et al. Ghrelin inhibits the development of mouse preimplantation embryos in vitro. Endocrinology. 2003;144:2623–2633

 P.D. has nothing to disclose. L.M. has nothing to disclose. D.R. has nothing to disclose. E.B. has nothing to disclose. P.K. has nothing to disclose. P.I.R. has nothing to disclose. J.M. has nothing to disclose.

 This work was supported by grants from the Polish Ministry of Science and Higher Education (4T11E 007 25) and the Medical University of Warsaw (1M15/N/07).

PII: S0015-0282(08)03867-3

doi: 10.1016/j.fertnstert.2008.09.002

Fertility and Sterility
Volume 92, Issue 6 , Pages 1844-1849 , December 2009

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