Sonic hedgehog, a morphogen in penile development

描述（由申请人提供）：拟议的研究将检查 Sonic hedgehog（Shh）在阴茎发育中的作用以及 糖尿病中的这一途径导致勃起功能障碍。嘘是一个秘密 与间充质-上皮相互作用密切相关的糖肽 发育中的组织。我们将展示初步证据， 阴茎体在阴茎发育过程中和成年后受到神经调节， 并建议确定糖尿病神经病变对表达的影响， 和Shh在躯体中的活动。糖尿病是一种常见的风险 勃起功能障碍的因素，这是一个毁灭性的病理发展 这影响了1000万到3000万美国人，花费超过1.5亿美元， 仅住院泌尿科护理（1985年美元）。虽然血管病和 神经病变是DM自然史中常见的并发症， 糖尿病性阳痿的病因尚不清楚。我们将检验这个假设 神经Shh信号是建立和维持正常 糖尿病患者阴茎形态学改变与勃起功能障碍 神经病是由Shh的稳态功能破坏引起的。 通路该提案的力量在于其提供新颖且 对糖尿病引起勃起的机制的至关重要的见解 功能这可能为新的治疗方法提供基础， 这一并发症，并可能提供其他神经血管的附带见解 糖尿病并发症。 所提出的实验非常适合满足本RFA的目标 由于利用新颖和创新技术来推进我们目前 了解泌尿生殖发育的一个方面，特别是神经如何 出生后阴茎形态发生过程中的Shh信号建立了阴茎勃起 勃起所需的海绵体完整性重新建立此信令 pathway为勃起功能障碍的治疗提供了巨大的希望。知识 在这些研究中获得的结果可以用于研究神经输入的作用 在建立组织身份和检查神经病变的功能， 疾病

DESCRIPTION (provided by applicant): The proposed research will examine the role of Sonic hedgehog (Shh) in penile development and the dysregulation of this pathway in diabetes induced erectile dysfunction. Shh is a secreted glycopeptide that is critically relevant in mesenchymal-epithelial interaction in developing tissues. We will show preliminary evidence that Shh signaling in the corpora is neurally regulated during penile development and in the adult, and propose to determine the impact of diabetic neuropathy on the expression and activity of Shh in corporal bodies. Diabetes mellitus is a common risk factor for erectile dysfunction, which is a devastating pathologic development that effects 10-30 million American men and costs in excess of $150 million for inpatient urologic care alone (1985 dollars). Although angiopathy and neuropathy are frequent complications in the natural history of DM, the precise cause of diabetic impotence remains unknown. We will examine the hypothesis that neural Shh signaling is elemental in establishing and maintaining normal penile morphology and that erectile dysfunction associated with diabetic neuropathy results from disruption of the homeostatic functions of the Shh pathway. The power of this proposal is its potential to provide novel and critically important insight into the mechanism of diabetes induced erectile function. This may provide the basis for new treatments to prevent or treat this complication and may provide collateral insights into other neurovascular complications of diabetes. The proposed experiments are ideally suited to satisfy the goals of this RFA since novel and innovative technology is utilized to advance our current understanding of one aspect of urogenital development, specifically how neural Shh signaling during postnatal morphogenesis of the penis establishes corporal cavernosal integrity required for erection. Re-establishment of this signaling pathway offers great promise for erectile dysfirnction treatment. Knowledge gained in these studies may be applied to investigate the role of neural input in establishing tissue identity and examining the function of neuropathy in disease.