Cargando…

Testosterone regulates the expression and functional activity of sphingosine‐1‐phosphate receptors in the rat corpus cavernosum

The bioactive lipid sphingosine‐1‐phosphate (S1P) regulates smooth muscle (SM) contractility predominantly via three G protein‐coupled receptors. The S1P1 receptor is associated with nitric oxide (NO)‐mediated SM relaxation, while S1P2 & S1P3 receptors are linked to SM contraction via activation...

Descripción completa

Detalles Bibliográficos
Autores principales: Yin, Jing, Guo, Yu‐ming, Chen, Ping, Xiao, He, Wang, Xing‐huan, DiSanto, Michael E, Zhang, Xin‐hua
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824404/
https://www.ncbi.nlm.nih.gov/pubmed/29266713
http://dx.doi.org/10.1111/jcmm.13416
_version_ 1783302018360672256
author Yin, Jing
Guo, Yu‐ming
Chen, Ping
Xiao, He
Wang, Xing‐huan
DiSanto, Michael E
Zhang, Xin‐hua
author_facet Yin, Jing
Guo, Yu‐ming
Chen, Ping
Xiao, He
Wang, Xing‐huan
DiSanto, Michael E
Zhang, Xin‐hua
author_sort Yin, Jing
collection PubMed
description The bioactive lipid sphingosine‐1‐phosphate (S1P) regulates smooth muscle (SM) contractility predominantly via three G protein‐coupled receptors. The S1P1 receptor is associated with nitric oxide (NO)‐mediated SM relaxation, while S1P2 & S1P3 receptors are linked to SM contraction via activation of the Rho‐kinase pathway. This study is to determine testosterone (T) modulating the expression and functional activity of S1P receptors in corpus cavernosum (CC). Adult male Sprague‐Dawley rats were randomly divided into three groups: sham‐operated controls, surgical castration and T supplemented group. Serum S1P levels were detected by high‐performance liquid chromatography. The expression of S1P1‐3 receptors and sphingosine kinases was detected by real‐time RT‐PCR. In vitro organ bath contractility and in vivo intracavernous pressure (ICP) measurement were also performed. T deprivation significantly decreased ICP rise. Meanwhile, surgical castration induced a significant increase in serum S1P level and the expression of S1P2‐3 receptors by twofold (P < 0.05) but a decrease in the expression of S1P1 receptor. Castration also augmented exogenous phenylephrine (PE), S1P, S1P1,3 receptor agonist FTY720‐P contractility and S1P2‐specific antagonist JTE013 relaxation effect. T supplemented could restore the aforementioned changes. We provide novel data that castration increased serum S1P concentration and up‐regulated the expression of S1P2‐3 receptors in CC. Consistently, agonizing S1P receptors induced CCSM contraction and antagonizing mediated relaxation were augmented. This provides the first clear evidence that S1P system dysregulation may contribute to hypogonadism‐related erectile dysfunction (ED), and S1P receptors may be expected as a potential target for treating ED.
format Online
Article
Text
id pubmed-5824404
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-58244042018-03-01 Testosterone regulates the expression and functional activity of sphingosine‐1‐phosphate receptors in the rat corpus cavernosum Yin, Jing Guo, Yu‐ming Chen, Ping Xiao, He Wang, Xing‐huan DiSanto, Michael E Zhang, Xin‐hua J Cell Mol Med Original Articles The bioactive lipid sphingosine‐1‐phosphate (S1P) regulates smooth muscle (SM) contractility predominantly via three G protein‐coupled receptors. The S1P1 receptor is associated with nitric oxide (NO)‐mediated SM relaxation, while S1P2 & S1P3 receptors are linked to SM contraction via activation of the Rho‐kinase pathway. This study is to determine testosterone (T) modulating the expression and functional activity of S1P receptors in corpus cavernosum (CC). Adult male Sprague‐Dawley rats were randomly divided into three groups: sham‐operated controls, surgical castration and T supplemented group. Serum S1P levels were detected by high‐performance liquid chromatography. The expression of S1P1‐3 receptors and sphingosine kinases was detected by real‐time RT‐PCR. In vitro organ bath contractility and in vivo intracavernous pressure (ICP) measurement were also performed. T deprivation significantly decreased ICP rise. Meanwhile, surgical castration induced a significant increase in serum S1P level and the expression of S1P2‐3 receptors by twofold (P < 0.05) but a decrease in the expression of S1P1 receptor. Castration also augmented exogenous phenylephrine (PE), S1P, S1P1,3 receptor agonist FTY720‐P contractility and S1P2‐specific antagonist JTE013 relaxation effect. T supplemented could restore the aforementioned changes. We provide novel data that castration increased serum S1P concentration and up‐regulated the expression of S1P2‐3 receptors in CC. Consistently, agonizing S1P receptors induced CCSM contraction and antagonizing mediated relaxation were augmented. This provides the first clear evidence that S1P system dysregulation may contribute to hypogonadism‐related erectile dysfunction (ED), and S1P receptors may be expected as a potential target for treating ED. John Wiley and Sons Inc. 2017-12-20 2018-03 /pmc/articles/PMC5824404/ /pubmed/29266713 http://dx.doi.org/10.1111/jcmm.13416 Text en © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Yin, Jing
Guo, Yu‐ming
Chen, Ping
Xiao, He
Wang, Xing‐huan
DiSanto, Michael E
Zhang, Xin‐hua
Testosterone regulates the expression and functional activity of sphingosine‐1‐phosphate receptors in the rat corpus cavernosum
title Testosterone regulates the expression and functional activity of sphingosine‐1‐phosphate receptors in the rat corpus cavernosum
title_full Testosterone regulates the expression and functional activity of sphingosine‐1‐phosphate receptors in the rat corpus cavernosum
title_fullStr Testosterone regulates the expression and functional activity of sphingosine‐1‐phosphate receptors in the rat corpus cavernosum
title_full_unstemmed Testosterone regulates the expression and functional activity of sphingosine‐1‐phosphate receptors in the rat corpus cavernosum
title_short Testosterone regulates the expression and functional activity of sphingosine‐1‐phosphate receptors in the rat corpus cavernosum
title_sort testosterone regulates the expression and functional activity of sphingosine‐1‐phosphate receptors in the rat corpus cavernosum
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824404/
https://www.ncbi.nlm.nih.gov/pubmed/29266713
http://dx.doi.org/10.1111/jcmm.13416
work_keys_str_mv AT yinjing testosteroneregulatestheexpressionandfunctionalactivityofsphingosine1phosphatereceptorsintheratcorpuscavernosum
AT guoyuming testosteroneregulatestheexpressionandfunctionalactivityofsphingosine1phosphatereceptorsintheratcorpuscavernosum
AT chenping testosteroneregulatestheexpressionandfunctionalactivityofsphingosine1phosphatereceptorsintheratcorpuscavernosum
AT xiaohe testosteroneregulatestheexpressionandfunctionalactivityofsphingosine1phosphatereceptorsintheratcorpuscavernosum
AT wangxinghuan testosteroneregulatestheexpressionandfunctionalactivityofsphingosine1phosphatereceptorsintheratcorpuscavernosum
AT disantomichaele testosteroneregulatestheexpressionandfunctionalactivityofsphingosine1phosphatereceptorsintheratcorpuscavernosum
AT zhangxinhua testosteroneregulatestheexpressionandfunctionalactivityofsphingosine1phosphatereceptorsintheratcorpuscavernosum