Urokinase-type plasminogen activator and insulin-like growth factor-binding protein 3 mRNA expression in endometriotic lesions and eutopic endometrium: implications for the pathophysiology of endometriosis.
The peritoneal fluid of women with endometriosis contains an increased insulin-like growth factor 1 (IGF-1) bioavailability, which is produced by limited hydrolysis of urokinase-type plasminogen activator (uPA) on IGF-binding protein 3 (IGFBP-3). Recently, IGF-1 was shown to inhibit apoptosis of endometrial-like cells in vitro, suggesting that a microenvironment of increased IGF-1 bioavailability can optimize the survival of endometrial cells grown ectopically. Here the expression of mRNA of IGFBP-3 and uPA in tissue biopsies from eutopic endometrium and endometriotic lesions obtained at laparoscopy from women with endometriosis have been analyzed, and it is documented that both IGFBP-3 and uPA mRNA expression are increased from 3- to 10-fold in endometriotic lesions versus eutopic endometrium. Consequently, the necessary components (uPA and IGFBP-3 expression) of endocrine/autocrine/paracrine enhancement of local IGF bioavailability mediated by uPA hydrolysis of the IGFBP-3 were present in endometriotic lesions. These data possibly explain the origin of the increased content of uPA activity, IGF-1 bioavailability, and NH(2)-truncated forms of IGFBP-3 in the peritoneal fluid of women with endometriosis.
Lembessis
Peter
P
Department of Experimental Physiology, University of Athens Medical School, 75 Micras Athens, Goudi-Athens 115 27, Greece.
Milingos
Spyros
S
Michalas
Stelios
S
Milingos
Dimitris
D
Creatsas
George
G
Sourla
Antigone
A
Koutsilieris
Michael
M
D001202:Ascitic Fluid; D001707:Biopsy, Needle; D016022:Case-Control Studies; D046508:Culture Techniques; D004715:Endometriosis / Q000235:genetics / Q000473:pathology*; D005260:Female; D005786:Gene Expression Regulation; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000032:analysis / Q000235:genetics*; D011336:Probability; D012333:RNA, Messenger / Q000032:analysis; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis / Q000235:genetics*
D005819:Genetic Markers; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D014568:Urokinase-Type Plasminogen Activator