The cause and effect relationship between ectopic endometrial cell growth and characteristic local inflammatory response is unknown but is probably of fundamental importance in endometriosis (E). We are proposing to investigate this relationship by studying the interaction of inflammatory macrophages and endometrial stromal cells both in experiments in vitro and in ectopic E implants. The proposed studies are based on our early observations documenting phenotypic and secretory differences in E peritoneal macrophages as compared to those of normal women (N). Since E peritoneal macrophages release increased levels of growth factor(s) and connective tissue component(s) (fibronectin), a similar potential exists for macrophages in ectopic E implants. As a simplified in vitro model for E, we will examine the steady-state mRNA expression and production and inflammation mediators/growth factors and connective tissue components by interacting monocytes and stromal cells. In a limited fashion, similar experiments will then be carried out by using N and E peritoneal macrophages in the place of monocytes. In the view that sex steroids have potential of influencing both endometrial stromal and inflammatory cells, effect of physiologic concentrations of estradiol and progesterone and pharmacologic concentrations of danazol in these interactions will be assessed. In addition, direct effects of recombinant mediators/growth factors on stromal cell proliferation will be investigated in fresh primary cultures of endometrial stromal cells, endometrial stromal cell lines, and immunohistologic procedures will be employed in identification and characterization of inflammatory macrophages and their spatial relationship to proliferating stromal cells in ectopic E implants. Similar techniques combined with in situ hybridization will then determine the pattern of expression/production of inflammation mediators or connective tissue components by in situ macrophages/stromal cells in various morphologically distinct E lesions. The completion of these studies will enhance our understanding of the role of cellular interactions in the possibly self- perpetuating cycle of E-implant proliferation and associated inflammatory reaction.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD021546-06
Application #
3320479
Study Section
Reproductive Endocrinology Study Section (REN)
Project Start
1987-07-01
Project End
1992-11-30
Budget Start
1990-12-01
Budget End
1991-11-30
Support Year
6
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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Hammond, M G; Oh, S T; Anners, J et al. (1993) The effect of growth factors on the proliferation of human endometrial stromal cells in culture. Am J Obstet Gynecol 168:1131-6;discussion 1136-8
Van Le, L; Oh, S T; Anners, J A et al. (1992) Interleukin-1 inhibits growth of normal human endometrial stromal cells. Obstet Gynecol 80:405-9
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Surrey, E S; Halme, J (1992) Direct effects of medroxyprogesterone acetate, danazol, and leuprolide acetate on endometrial stromal cell proliferation in vitro. Fertil Steril 58:273-8
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Surrey, E S; Halme, J (1991) Effect of platelet-derived growth factor on endometrial stromal cell proliferation in vitro: a model for endometriosis? Fertil Steril 56:672-9
Haskill, S; Martin, G; Van Le, L et al. (1991) cDNA cloning of an intracellular form of the human interleukin 1 receptor antagonist associated with epithelium. Proc Natl Acad Sci U S A 88:3681-5
Surrey, E S; Halme, J (1990) Effect of peritoneal fluid from endometriosis patients on endometrial stromal cell proliferation in vitro. Obstet Gynecol 76:792-7
Sporn, S A; Eierman, D F; Johnson, C E et al. (1990) Monocyte adherence results in selective induction of novel genes sharing homology with mediators of inflammation and tissue repair. J Immunol 144:4434-41

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