Molecular Human Reproduction, Vol. 8, No. 12, 1053-1064,
December 2002
© 2002 European Society of Human Reproduction and Embryology
Molecular endocrinology |
Expression and regulation of endothelin-1 and its receptors in human penile smooth muscle cells
1 Andrology Unit and 2 Endocrine Unit, Department of Clinical Physiopathology, 3 Department of Anatomy, Histology and Forensic Medicine and 4 Department of Pharmacology, University of Florence, 50139 Florence, Italy
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 
smooth muscle actin and phosphodiesterase type 5A3 along with hallmarks of androgen-dependent cells (androgen receptor and 5 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-ß1 (TGF-ß1), interleukin-1 (IL-1), 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-ß1; 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.
corpus cavernosum/endothelin/erection/hypoxia/smooth muscle cells
5 To whom correspondence should be addressed at Dipartimento di Fisiopatologia Clinica, Unità di Andrologia, Università di Firenze, Viale Pieraccini, n° 6, 50139 Florence, Italy. E-mail: m.maggi{at}dfc.unifi.it
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