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

Peter Lembessis, Milingos S, Spyros Milingos, Michalas S, Stelios Michalas, S. Michalas, Milingos D, DIMITRIS MILINGOS, George Creatsas, Creatsas G, Antigone Sourla, Sourla A, Michael Koutsilieris, Koutsilieris M
Annals of the New York Academy of Sciences · 2003 · vol. 997(1) , pp. 223–228 · doi:10.1196/annals.1290.025 · PMID:14644829 · W1973949788
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Endometriotic lesions exhibit increased mRNA expression of uPA and IGFBP-3 compared to eutopic endometrium, potentially explaining increased local IGF bioavailability.

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Abstract

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.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Genetic Predisposition to Disease Genetic Predisposition to Disease Insulin-Like Growth Factor Binding Protein 3 Urokinase-Type Plasminogen Activator Ascitic Fluid Ascitic Fluid Biopsy, Needle Biopsy, Needle Case-Control Studies Case-Control Studies Culture Techniques Culture Techniques Endometriosis Endometriosis Endometriosis Female Female Gene Expression Regulation Gene Expression Regulation

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