Expressionsmuster und zelluläre Lokalisation des TGF-β1 und seiner Ko-Faktoren in humanem Endometrium und bei der Endometriose

In: Geburtshilfe und Frauenheilkunde · 2001 · vol. 61(10) , pp. 778–783 · doi:10.1055/s-2001-18367 · W2048985061
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This study investigated the expression patterns and cellular localization of TGF-β1 and its co-factors in human endometrium and endometriosis to understand their roles in tissue growth and pathogenesis.

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Abstract

Die Erkrankung Endometriose stellt sowohl in Bezug auf die noch unvollständig geklärte Entstehung und Pathogenese, als auch im Hinblick auf die diagnostische Beurteilung und adäquate Therapie eine große Herausforderung dar. Im eutopen Endometrium scheint Transforming Growth Factor β1 (TGF-β1) über para- und autokrine Effekte beim Wachstum und der Differenzierung des Gewebes eine Schlüsselrolle zu spielen. Die molekularen Mechanismen, die bei der Endometrioseerkrankung zu einem häufig invasiv-destruierenden Wachstum führen, sind weitgehend unbekannt.
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Abstract

Objective Endometriosis represents a challenge because its mostly unknown etiology and pathogenesis causes difficulties in diagnostic assessment as well as in choosing the appropriate therapy. In eutopic endometrium, TGF-β1 seems to play a crucial part in tissue growth and differentiation by para- and autocrine mechanisms. So far, little is known about the molecular mechanisms leading to invasive and destructive growth in endometriosis.

Methods

Therefore we examined the expression and cellular localization of TGF-β1 including its inactive precursor LAP, its binding protein LTBP-1 and the expression of TGF-β-R-I in vitro and in vivo in eutopic and ectopic human endometrium (endometriosis).

Results

Both in eutopic and ectopic endometrium, all four proteins were found to be synthesized predominantly in the epithelium whereas the mRNA of TGF-β1, TGF-β-R-I and LTBP-1 was expressed at equal amounts in stromal and epithelial fractions. LTBP-1 protein expression was found to be significantly higher in endometriosis compared with eutopic endometrium.

Conclusion

The increased synthesis of LTBP-1 in endometriosis compared to eutopic endometrium, that results in a higher secretion of TGF-β1, can possibly explain the elevated adhesive and invasive activity of endometriotic lesions. Schlüsselwörter Endometriose - Endometrium - LTBP-1 - TGF-β1 - Invasives Wachstum Key words Endometriosis - Endometrium - LTBP-1 - TGF-β1 - Invasive growth Literatur - 1 Arici A, MacDonald P C, Casey M L. Modulation of the levels of transforming growth factor beta messenger ribonucleic acids in human endometrial stromal cells. Biol Reprod. 1996; 54 463-469 - 2 Bühler K. Sicherheit und Verträglichkeit von GnRH-Agonisten in der Gynäkologie. Zentralbl Gynäkol. 1999; 121 344-348 - 3 Chegini N, Gold L I, Williams R S. et al . Localization of transforming growth factor beta isoforms TGF-beta 1, TGF-beta 2, and TGF-beta 3 in surgically induced pelvic adhesions in the rat. Obstet Gynecol. 1994; 83 449-454 - 4 Croxtall J D, Jamil A, Ayub M. et al . 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Cell Growth Differ. 1994; 5 919-935 - 27 Tamura M, Fukaya T, Enomoto A. et al . Transforming growth factor-beta isoforms and receptors in endometriotic cysts of the human ovary. Am J Reprod Immunol. 1999; 42 160-167 - 28 Tang X M, Zhao Y, Rossi M J. et al . Expression of transforming growth factor-beta (TGF beta) isoforms and TGF beta type II receptor messenger ribonucleic acid and protein, and the effect of TGF beta on endometrial stromal cell growth and protein degradation in vitro. Endocrinology. 1994; 135 450-459 - 29 Van L J, Resibois A, Adler M. et al . Localization of transforming growth factor-beta 1 precursor and latent TGF-beta 1 binding protein in colorectal adenomas. Dig Dis Sci. 1996; 41 1741-1748 - 30 Witz C A, Monotoya-Rodriguez I A, Schenken R S. Whole explants of peritoneum and endometrium: a novel model of the early endometriosis lesion. Fertil Steril. 1999; 71 56-60 - 31 Zajchowski D, Band V, Pauzie N. et al . Expression of growth factors and oncogenes in normal and tumor-derived human mammary epithelial cells. Cancer Res. 1988; 48 7041-7047 Ärztlicher Direktor Prof. Dr. med. L. Kiesel Klinik und Poliklinik Frauenheilkunde und Geburtshilfe Universitätsklinikum Münster Albert-Schweitzer-Straße 33 48129 Münster Email: [email protected]

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