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
Andrology Unit, Department of Clinical Physiopathology, University of Florence, 50139 Florence, Italy.
Mol Hum Reprod. 2002 Dec;8(12):1053-64. doi: 10.1093/molehr/8.12.1053.
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 alpha smooth muscle actin and phosphodiesterase type 5A3 along with hallmarks of androgen-dependent cells (androgen receptor and 5alpha 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-beta1 (TGF-beta1), interleukin-1alpha (IL-1alpha), 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-beta1; 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.
我们首次报道，阴茎平滑肌细胞（SMC）不仅对内皮素 -1（ET-1）有反应，而且还能合成ET-1，ET-1是SMC活性的主要调节因子之一。免疫组织化学研究表明，除了内皮细胞（EC）外，成年和胎儿阴茎的SMC也表达ET-1及其转化酶ECE-1。相应地，成年阴茎基质细胞培养物也表达这些基因。我们还制备并鉴定了来自人类胎儿的阴茎SMC。这些细胞表达SMC特异性标志物，如α平滑肌肌动蛋白和5型磷酸二酯酶A3，以及雄激素依赖性细胞的标志物（雄激素受体和2型5α还原酶）。人类胎儿阴茎SMC（hfPSMC）对ET-1免疫阳性并释放ET-1。hfPSMC中ET-1的表达受到多种因素的强烈上调，如转化生长因子 -β1（TGF-β1）、白细胞介素 -1α（IL-1α）、ET-1自身以及长时间（24小时）缺氧。后一种情况不仅影响ET-1的表达，还影响其反应性。在正常氧张力下，hfPSMC对ET-1的反应是通过内皮素 -A受体和TGF-β1介导的增殖减少；然而，在缺氧期间，ET-1刺激细胞生长。相应地，长时间缺氧上调了内皮素 -B受体mRNA的表达。总之，我们的结果表明，在阴茎组织中SMC产生ET-1，并且这种产生受到参与阴茎生理和组织重塑的因素的调节。此外，我们鉴定的hfPSMC可能是体外研究人类勃起过程生化方面的有用模型。
