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To the Editors: We would like to thank Choy and Yip for their letter and their interest in our work.1Poncet S. Meyer S. Richard C. Aubert J.D. Juillerat-Jeanneret L. The expression and function of the endothelin system in contractile properties of vaginal myofibroblasts of women with uterovaginal prolapse.Am J Obstet Gynecol. 2005; 192: 426-432Abstract Full Text Full Text PDF PubMed Scopus (27) Google Scholar First of all, we have an initial comment: we did not report that expression of endothelin-1 (ET-1), but that addition of exogenous ET-1, decreased uterovaginal myofibroblast contraction. In the ET-1–mediated contraction of skin myofibroblasts, ET-1 source was hypothesized to be the epithelial cells, and not the fibroblasts. We never detected the secretion of ET-1 by human uterovaginal and other (unpublished experiments) myofibroblast population in culture, whereas ET-1 mRNA could be found by reverse transcription-polymerase chain reaction. Therefore, we did not consider potential ET-1 polymorphism as a useful marker to predict postpartum disorders, and we did not look for either ET-1 polymorphism, or ET-2 or ET-3 expression in uterovaginal myofibroblasts and tissue. We have been studying the endothelin system in human diseases for many years, and we agree with Choy and Yip that ET-1 is mainly thought of as a potent vasoconstrictor. However, under some circumstances, in response to ET-1, initial vasorelaxation, generally accepted to be endothelin receptor B (ETB)-mediated, can also be observed. We also agree with Choy and Yip that in skin myofibroblasts in culture, ET-1 was demonstrated to be a promoter of constriction, and, in fact, our initial working hypothesis was that ET-1 had similar effect in uterovaginal myofibroblasts, which was dysfunctioning in postpartum disorders. However, in our hands and under our experimental conditions, ET-1 was rather a relaxation-inducing than a contraction-inducing factor in human uterovaginal myofibroblasts. One plausible explanation resides in the fact that ET-1 mediates constriction in vascular cells and skin fibroblasts via the endothelin receptor A (ETA) receptor, whereas in uterovaginal myofibroblasts, we observed only functional ETB receptor. In this context, it is interesting to note that we also observed selective induction of ETB expression in perivascular myofibroblasts in human cancer, which may be linked to defects in vasoconstriction in human tumor vasculature.2Egidy G. Juillerat-Jeanneret L. Jeannin J.F. Korth P. Bosman F.T. Pinet F. Modulation of human colon tumor-stromal interactions by the endothelin system.Am J Pathol. 2000; 157: 1863-1874Abstract Full Text Full Text PDF PubMed Scopus (75) Google Scholar Another potential explanation which cannot be excluded is that variants of either ETA or ETB are expressed by uterovaginal myofibroblasts, since variants of both receptors have been described.3Shyamala V. Moulthrop T.H.M. Stratton-Thomas J. Tekamp-Olson P. Two distinct human endothelin B receptors generated by alternative splicing from a single gene.Cell Mol Biol Res. 1994; 40: 285-296PubMed Google Scholar, 4Zhang Y.F. Jeffery S. Burchill S.A. Berry P.A. Kaski J.C. Carter N.D. Truncated human endothelin receptor A produced by alternative splicing and its expression in melanoma.Br J Cancer. 1998; 78: 1141-1146Crossref PubMed Scopus (16) Google Scholar We did not specifically look for receptor variants in uterovaginal myofibroblasts, but detected these expressions in other human cell populations [Berger et al, submitted for publication]. Therefore, we would propose that in postpartum disorders, if alternate variants have to be searched, ETA, or less likely, ETB might be a more appropriate target than ET-1. Necessary to evaluate the possible involvement of endothelin-1 gene polymorphisms in urinary dysfunction?American Journal of Obstetrics & GynecologyVol. 194Issue 1PreviewTo the Editors: In a recent issue of the American Journal of Obstetrics and Gynecology, Poncet et al reported that genital myofibroblasts of women with uterovaginal prolapse are poorly contractile, and expression of endothelin-1 (ET-1) further decreases vaginal myofibroblast contraction. They pointed out that significant inhibitory effect in contractile properties of vaginal myofibroblasts was prominent at high ET-1 concentration among women with uterovaginal prolapse (Table III and Figure 4).1 Endothelin-1 (ET-1), which acts through endothelin A and B receptors, has been demonstrated as being a potent vasoconstrictor. Full-Text PDF