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Testosterone positively regulates vagina NO-induced relaxation: an experimental study in rats

PURPOSE: Female sexual response involves a complex interplay between neurophysiological mechanisms and the nitric oxide (NO)-mediated relaxation of clitoris and vagina. The aim of this study was to evaluate sex steroids regulation of the relaxant pathway in vagina, using a validated animal model. ME...

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Autores principales: Cellai, I., Filippi, S., Comeglio, P., Cipriani, S., Maseroli, E., Di Stasi, V., Todisco, T., Marchiani, S., Tamburrino, L., Villanelli, F., Vezzani, S., Corno, C., Fambrini, M., Guarnieri, G., Sarchielli, E., Morelli, A., Rastrelli, G., Maggi, M., Vignozzi, L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9098587/
https://www.ncbi.nlm.nih.gov/pubmed/35072927
http://dx.doi.org/10.1007/s40618-022-01743-4
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author Cellai, I.
Filippi, S.
Comeglio, P.
Cipriani, S.
Maseroli, E.
Di Stasi, V.
Todisco, T.
Marchiani, S.
Tamburrino, L.
Villanelli, F.
Vezzani, S.
Corno, C.
Fambrini, M.
Guarnieri, G.
Sarchielli, E.
Morelli, A.
Rastrelli, G.
Maggi, M.
Vignozzi, L.
author_facet Cellai, I.
Filippi, S.
Comeglio, P.
Cipriani, S.
Maseroli, E.
Di Stasi, V.
Todisco, T.
Marchiani, S.
Tamburrino, L.
Villanelli, F.
Vezzani, S.
Corno, C.
Fambrini, M.
Guarnieri, G.
Sarchielli, E.
Morelli, A.
Rastrelli, G.
Maggi, M.
Vignozzi, L.
author_sort Cellai, I.
collection PubMed
description PURPOSE: Female sexual response involves a complex interplay between neurophysiological mechanisms and the nitric oxide (NO)-mediated relaxation of clitoris and vagina. The aim of this study was to evaluate sex steroids regulation of the relaxant pathway in vagina, using a validated animal model. METHODS: Subgroups of OVX Sprague–Dawley rats were treated with 17β-estradiol, testosterone, or testosterone and letrozole, and compared with a group of intact animals. Masson’s trichrome staining was performed for morphological evaluation of the distal vaginal wall, in vitro contractility studies investigated the effect of OVX and in vivo treatments on vaginal smooth muscle activity. RNA from vaginal tissue was analyzed by semi-quantitative RT-PCR. RESULTS: Immunohistochemical analysis showed that OVX induced epithelial and smooth muscle structural atrophy, testosterone and testo + letrozole increased the muscle bundles content and organization without affecting the epithelium while 17β-estradiol mediated the opposite effects. In vitro contractility studies were performed on noradrenaline pre-contracted vaginal strips from each experimental group. Acetylcholine (0.001–10 µM) stimulation induced a concentration-dependent relaxation, significantly reduced by NO-synthase inhibitor L-NAME and by guanylate cyclase inhibitor ODQ. OVX resulted in a decreased responsiveness to acetylcholine, restored by testosterone, with or without letrozole, but not by 17β-estradiol. OVX sensitivity to the NO-donor SNP was higher than in the control. Vardenafil, a PDE5 inhibitor, enhanced SNP effect in OVX + testosterone as well as in control, as supported by RNA expression analysis. CONCLUSIONS: Our study demonstrates that testosterone improves the NO-mediated smooth muscle vaginal cells relaxation confirming its role in maintaining the integrity of muscular relaxant machinery.
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spelling pubmed-90985872022-05-14 Testosterone positively regulates vagina NO-induced relaxation: an experimental study in rats Cellai, I. Filippi, S. Comeglio, P. Cipriani, S. Maseroli, E. Di Stasi, V. Todisco, T. Marchiani, S. Tamburrino, L. Villanelli, F. Vezzani, S. Corno, C. Fambrini, M. Guarnieri, G. Sarchielli, E. Morelli, A. Rastrelli, G. Maggi, M. Vignozzi, L. J Endocrinol Invest Original Article PURPOSE: Female sexual response involves a complex interplay between neurophysiological mechanisms and the nitric oxide (NO)-mediated relaxation of clitoris and vagina. The aim of this study was to evaluate sex steroids regulation of the relaxant pathway in vagina, using a validated animal model. METHODS: Subgroups of OVX Sprague–Dawley rats were treated with 17β-estradiol, testosterone, or testosterone and letrozole, and compared with a group of intact animals. Masson’s trichrome staining was performed for morphological evaluation of the distal vaginal wall, in vitro contractility studies investigated the effect of OVX and in vivo treatments on vaginal smooth muscle activity. RNA from vaginal tissue was analyzed by semi-quantitative RT-PCR. RESULTS: Immunohistochemical analysis showed that OVX induced epithelial and smooth muscle structural atrophy, testosterone and testo + letrozole increased the muscle bundles content and organization without affecting the epithelium while 17β-estradiol mediated the opposite effects. In vitro contractility studies were performed on noradrenaline pre-contracted vaginal strips from each experimental group. Acetylcholine (0.001–10 µM) stimulation induced a concentration-dependent relaxation, significantly reduced by NO-synthase inhibitor L-NAME and by guanylate cyclase inhibitor ODQ. OVX resulted in a decreased responsiveness to acetylcholine, restored by testosterone, with or without letrozole, but not by 17β-estradiol. OVX sensitivity to the NO-donor SNP was higher than in the control. Vardenafil, a PDE5 inhibitor, enhanced SNP effect in OVX + testosterone as well as in control, as supported by RNA expression analysis. CONCLUSIONS: Our study demonstrates that testosterone improves the NO-mediated smooth muscle vaginal cells relaxation confirming its role in maintaining the integrity of muscular relaxant machinery. Springer International Publishing 2022-01-24 2022 /pmc/articles/PMC9098587/ /pubmed/35072927 http://dx.doi.org/10.1007/s40618-022-01743-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Article
Cellai, I.
Filippi, S.
Comeglio, P.
Cipriani, S.
Maseroli, E.
Di Stasi, V.
Todisco, T.
Marchiani, S.
Tamburrino, L.
Villanelli, F.
Vezzani, S.
Corno, C.
Fambrini, M.
Guarnieri, G.
Sarchielli, E.
Morelli, A.
Rastrelli, G.
Maggi, M.
Vignozzi, L.
Testosterone positively regulates vagina NO-induced relaxation: an experimental study in rats
title Testosterone positively regulates vagina NO-induced relaxation: an experimental study in rats
title_full Testosterone positively regulates vagina NO-induced relaxation: an experimental study in rats
title_fullStr Testosterone positively regulates vagina NO-induced relaxation: an experimental study in rats
title_full_unstemmed Testosterone positively regulates vagina NO-induced relaxation: an experimental study in rats
title_short Testosterone positively regulates vagina NO-induced relaxation: an experimental study in rats
title_sort testosterone positively regulates vagina no-induced relaxation: an experimental study in rats
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9098587/
https://www.ncbi.nlm.nih.gov/pubmed/35072927
http://dx.doi.org/10.1007/s40618-022-01743-4
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