Bond Christopher, Tang Yi, Podlasek Carol A
Department of Urology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Biol Reprod. 2008 May;78(5):947-56. doi: 10.1095/biolreprod.107.064766. Epub 2008 Feb 6.
The role of sonic hedgehog (SHH) in maintaining corpora cavernosal morphology in the adult penis has been established; however, the mechanism of how SHH itself is regulated remains unclear. Since decreased SHH protein is a cause of smooth muscle apoptosis and erectile dysfunction (ED) in the penis, and SHH treatment can suppress cavernous nerve (CN) injury-induced apoptosis, the question of how SHH signaling is regulated is significant. It is likely that neural input is involved in this process since two models of neuropathy-induced ED exhibit decreased SHH protein and increased apoptosis in the penis. We propose the hypothesis that SHH abundance in the corpora cavernosa is regulated by SHH signaling in the pelvic ganglia, neural activity, or neural transport of a trophic factor from the pelvic ganglia to the corpora. We have examined each of these potential mechanisms. SHH inhibition in the penis shows a 12-fold increase in smooth muscle apoptosis. SHH inhibition in the pelvic ganglia causes significantly increased apoptosis (1.3-fold) and decreased SHH protein (1.1-fold) in the corpora cavernosa. SHH protein is not transported by the CN. Colchicine treatment of the CN resulted in significantly increased smooth muscle apoptosis (1.2-fold) and decreased SHH protein (1.3-fold) in the penis. Lidocaine treatment of the CN caused a similar increase in apoptosis (1.6-fold) and decrease in SHH protein (1.3-fold) in the penis. These results show that neural activity and a trophic factor from the pelvic ganglia/CN are necessary to regulate SHH protein and smooth muscle abundance in the penis.
音猬因子（SHH）在维持成年阴茎海绵体形态中的作用已得到证实；然而，SHH自身的调节机制仍不清楚。由于SHH蛋白减少是阴茎平滑肌凋亡和勃起功能障碍（ED）的一个原因，且SHH治疗可抑制海绵体神经（CN）损伤诱导的凋亡，因此SHH信号通路如何被调节这一问题具有重要意义。由于两种神经病变诱导的ED模型显示阴茎中SHH蛋白减少且凋亡增加，所以神经输入可能参与了这一过程。我们提出一个假说，即阴茎海绵体内SHH的丰度受盆腔神经节中的SHH信号通路、神经活动或从盆腔神经节到海绵体的营养因子的神经运输的调节。我们已经研究了这些潜在机制中的每一种。阴茎中SHH的抑制显示平滑肌凋亡增加了12倍。盆腔神经节中SHH的抑制导致海绵体中凋亡显著增加（1.3倍）且SHH蛋白减少（1.1倍）。SHH蛋白不是由CN运输的。用秋水仙碱处理CN导致阴茎中平滑肌凋亡显著增加（1.2倍）且SHH蛋白减少（1.3倍）。用利多卡因处理CN导致阴茎中凋亡有类似增加（1.6倍）且SHH蛋白减少（1.3倍）。这些结果表明，神经活动和来自盆腔神经节/CN的营养因子对于调节阴茎中SHH蛋白和平滑肌丰度是必要的。
