title: Effect of GnRH agonist therapy on the expression of human heat shock protein 70 in eutopic and ectopic endometria of women with endometriosis.
abstract: OBJECTIVE
  Human heat shock protein 70 (HSP70) has been reported to enhance Toll-like receptor 4-mediated pelvic inflammation and growth of endometriotic cells. However, information on tissue expression of HSP70 before and after treatment with estrogen suppressing agent is scanty. Here, we investigated tissue expression HSP70 in the eutopic/ectopic endometria of gonadotropin-releasing hormone agonist (GnRHa)-treated and -non-treated women with endometriosis.
  
  
  METHODS
  Biopsy specimens were collected from peritoneal lesions, cyst walls, and corresponding endometria of 20 women with peritoneal endometriosis, 35 women with ovarian endometrioma, and 15 control women during laparoscopy. Fifteen women with ovarian endometrioma were treated with GnRHa for a variable period of 4-6 months before laparoscopy. The immunoexpressions of HSP70 and CD68-positive macrophages (Mφ) in endometria, peritoneal lesions, and cyst walls were examined by immunohistochemistry. The immunoreactivity of HSP70 in tissues was analyzed by quantitative-histogram (Q-H) score.
  
  
  RESULTS
  Tissue expression of HSP70 was found to be the highest in the menstrual phase than in other phases of the menstrual cycle. A significantly higher immunoreactivity of HSP70 was found in the eutopic endometria of women with peritoneal and ovarian endometriosis than in controls and in opaque red lesions than in other peritoneal lesions. A significant correlation between Q-H scores of HSP70 and CD68-positive Mφ numbers was found in the endometria derived from women with peritoneal endometriosis (r=0.481) and in ovarian endometrioma (r=0.560) but not in control women. The Q-H scores of HSP70 expression were significantly lower in cyst walls, coexisting peritoneal lesions and corresponding endometria of women with ovarian endometrioma after GnRHa treatment comparing to similar tissues derived from women without GnRHa treatment.
  
  
  CONCLUSIONS
  These results suggest that as a marker of tissue stress reaction, immunoexpression of HSP70 was highly increased in pathological lesions and endometria of women with endometriosis and had a significant correlation with tissue inflammatory reaction. The higher tissue expression of HSP70 can be effectively suppressed after GnRHa treatment.
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Takehito
authors.initials: T
authors.lastname: Imamura
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan. Electronic address: nemokhan@nagasaki-u.ac.jp.
authors.forename: Khaleque N
authors.initials: KN
authors.lastname: Khan
authors.affiliation: Saiseikai Nagasaki Hospital, Nagasaki, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Fujishita
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Michio
authors.initials: M
authors.lastname: Kitajima
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Koichi
authors.initials: K
authors.lastname: Hiraki
authors.affiliation: Sasebo Chuo Hospital, Nagasaki, Japan.
authors.forename: Tadayuki
authors.initials: T
authors.lastname: Ishimaru
authors.affiliation: Department of Obstetrics and Gynecology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Masuzaki
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D004715:Endometriosis / Q000188:drug therapy* / Q000378:metabolism; D004717:Endometrium / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists*; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D008597:Menstrual Cycle / Q000187:drug effects* / Q000378:metabolism; D008598:Menstruation / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D010049:Ovarian Diseases / Q000188:drug therapy* / Q000378:metabolism; D010532:Peritoneal Diseases / Q000188:drug therapy* / Q000378:metabolism; D011446:Prospective Studies; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D018840:HSP70 Heat-Shock Proteins; D007987:Gonadotropin-Releasing Hormone
keywords: GnRH agonist; Inflammation; Ovarian endometrioma; Peritoneal endometriosis; Stress reaction