Department of Urology, Northwestern University Medical School, Chicago, IL 60611, USA.
J Sex Med. 2010 Mar;7(3):1116-25. doi: 10.1111/j.1743-6109.2009.01585.x. Epub 2009 Nov 19.
Smooth muscle apoptosis is a major contributing factor to erectile dysfunction (ED) development in prostatectomy and diabetic patients and animal models. A critical regulator of penile smooth muscle and apoptosis is Sonic hedgehog (SHH). The SHH protein is decreased in ED models and SHH treatment of cavernous nerve (CN) injured rats prevents smooth muscle apoptosis. A close association between androgen deficiency and ED has been suggested in the literature, but few studies have examined the molecular effects on penile smooth muscle and on known signaling mechanisms that regulate morphology. Aim. Examine testosterone and SHH interaction in eugonadal adult, adolescent and juvenile rats by performing castration studies and treatment with supraphysiological testosterone.
The eugonadal adult Sprague Dawley rats were either treated with testosterone for 7 or 14 days (N = 14) or were castrated for 4 or 7 days (N = 12). The juvenile rats were treated with testosterone for 8 days (N = 7). The adolescent rats were castrated and sacrificed at P88 (N = 8). The control rats had empty vehicle (N = 22) or sham surgery (N = 20).
The active form of SHH protein and mRNA were quantified by semi-quantitative immunohistochemical analysis and real-time reverse transcriptase polymerase chain reaction (RT-PCR).
Testosterone treatment did not alter SHH signaling in juvenile rats. Shh mRNA increased 3.2-fold and SHH protein increased 1.2-fold in rats castrated during puberty. In adult rats, castration decreased Shh mRNA 3.2-fold but did not alter SHH protein. Testosterone supplement in adult rats increased Shh mRNA 2.3-fold and decreased SHH protein 1.3-fold.
SHH signaling is independent of testosterone in normal juvenile rats and is sensitive to testosterone during adolescence, while testosterone supplement in the adult adversely impacts SHH signaling in a very similar manner to that observed with CN injury.
平滑肌细胞凋亡是前列腺切除术和糖尿病患者及动物模型中勃起功能障碍（ED）发展的主要因素。阴茎平滑肌和凋亡的关键调节因子是 Sonic hedgehog（SHH）。SHH 蛋白在 ED 模型中减少，SHH 治疗海绵体神经（CN）损伤大鼠可防止平滑肌细胞凋亡。文献中提示雄激素缺乏与 ED 密切相关，但很少有研究检查对阴茎平滑肌和已知调节形态的信号通路的分子作用。目的：通过进行去势研究和超生理剂量睾酮治疗，研究 eugonadal 成年、青少年和幼年大鼠中睾酮和 SHH 的相互作用。
eugonadal 成年 Sprague Dawley 大鼠分别接受睾酮治疗 7 或 14 天（n = 14）或去势 4 或 7 天（n = 12）。幼年大鼠接受睾酮治疗 8 天（n = 7）。青春期大鼠去势并在 P88 处死（n = 8）。对照组大鼠接受空载体（n = 22）或假手术（n = 20）。
采用半定量免疫组织化学分析和实时逆转录聚合酶链反应（RT-PCR）定量 SHH 蛋白和 mRNA 的活性形式。
睾酮治疗并未改变青春期大鼠的 SHH 信号通路。青春期去势大鼠 Shh mRNA 增加 3.2 倍，SHH 蛋白增加 1.2 倍。成年大鼠去势使 Shh mRNA 减少 3.2 倍，但不改变 SHH 蛋白。成年大鼠睾酮补充使 Shh mRNA 增加 2.3 倍，SHH 蛋白减少 1.3 倍。
SHH 信号通路在正常幼年大鼠中独立于睾酮，在青春期对睾酮敏感，而成年大鼠中睾酮补充以与 CN 损伤观察到的相似方式对 SHH 信号通路产生不利影响。
