Expression and regulation of endothelin-1 and its receptors in human penile smooth muscle cells

S. Granchi, G. B. Vannelli, L. Vignozzi, C. Crescioli, P. Ferruzzi, R. Mancina, M. C. Vinci, G. Forti, S. Filippi, M. Luconi, F. Ledda, M. Maggi

Research output: Contribution to journalArticle

Abstract

We report for the first time that penile smooth muscle cells (SMC) not only respond to, but also synthesize, endothelin-1 (ET-1), one of the main regulators of SMC activity. Immunohistochemical studies indicated that, beside endothelial cells (EC), SMC of the human adult and fetal penis also express ET-1 and its converting enzyme, ECE-1. Accordingly, cultures of adult penile stromal cells express these genes. We also prepared and characterized penile SMC from human fetuses. These cells express SMC specific markers such as α smooth muscle actin and phosphodiesterase type 5A3 along with hallmarks of androgen-dependent cells (androgen receptor and 5α reductase type 2). Human fetal penile SMC (hfPSMC) are immunopositive for ET-1 and release ET-1. ET-1 expression in hfPSMC was strongly increased by several factors such as transforming growth factor-β1 JGF-β1), interleukin-1α (IL-1α), ET-1 itself and prolonged (24 h) hypoxia. This latter condition not only affected ET-1 expression but also responsiveness. While at normal oxygen tension, hfPSMC responded to ET-1 with a decreased proliferation mediated by the endothelin-A receptors and TGF-β1; however, during hypoxia, ET-1 stimulated cell growth. Accordingly, prolonged hypoxia up-regulated endothelin-B receptor mRNA expression. In conclusion, our results indicate that in penile tissues SMC produce ET-1 and that such production is modulated by factors involved in penile physiology and tissue remodelling. In addition, the hfPSMC we have characterized might be a useful model for studying biochemical aspects of the human erectile process in vitro.

Original languageEnglish
Pages (from-to)1053-1064
Number of pages12
JournalMolecular Human Reproduction
Volume8
Issue number12
DOIs
Publication statusPublished - Dec 1 2002

Keywords

  • Corpus cavernosum
  • Endothelin
  • Erection
  • Hypoxia
  • Smooth muscle cells

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Genetics
  • Developmental Biology
  • Embryology
  • Cell Biology

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  • Cite this

    Granchi, S., Vannelli, G. B., Vignozzi, L., Crescioli, C., Ferruzzi, P., Mancina, R., Vinci, M. C., Forti, G., Filippi, S., Luconi, M., Ledda, F., & Maggi, M. (2002). Expression and regulation of endothelin-1 and its receptors in human penile smooth muscle cells. Molecular Human Reproduction, 8(12), 1053-1064. https://doi.org/10.1093/molehr/8.12.1053