Department of Urology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Department of Neurology, The Affiliated Hospital of Southwest Medical University, Luzhou, China.
Andrology. 2022 Sep;10(6):1189-1196. doi: 10.1111/andr.13202. Epub 2022 Jun 15.
The mechanism by which low androgen status inhibit erectile function has not yet been clearly elucidated. Neurogranin (Ng) is a Ca -sensitive calmodulin binding protein that is expressed in endothelial cells and regulates eNOS function.
To investigate whether low androgen status inhibit erectile function by regulating the Ng/CaN/AKT/eNOS pathway in the penile cavernous tissue of rats.
Thirty-six 8-week-old male Sprague-Dawley rats were randomly divided into six groups as follows (n = 6): 4-week control group (4w-control), 4-week castration group (4w-cast), 4-week castration+testosterone replacement group (4w-cast+T), 8-week control group (8w-control), 8-week castration group (8w-cast), and 8-week castration+testosterone replacement group (8w-cast+T). Four weeks and eight weeks after surgery, the ratio of the maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP) was examined. The level of NO and the expression of Ng, calcineurin (CaN), AKT, p-AKT(S473), eNOS, and p-eNOS(Ser1177) in the penile cavernous tissue of each group were determined.
Ng and CaN were mainly expressed in the membrane and cytoplasm of endothelial cells and smooth muscle cells in the penile cavernous tissue of rats. The ICPmax/MAP and the concentration of NO in the cast group were significantly lower than those in the control group and cast+T replacement group (p < 0.01). The expression of Ng and the ratios of p-AKT/AKT and p-eNOS/eNOS in the penile cavernous tissue of rats in the cast group were significantly lower than those in the control group and cast+T replacement group (p < 0.01). The expression of CaN in the penile cavernous tissue of rats in the cast group was significantly increased compared with that in the control group and the cast+T replacement group (p < 0.01).
Inhibiting the expression of Ng and subsequently upregulating the expression of CaN in the rat penile cavernous tissue was one of the upstream mechanisms of low androgen status inhibiting erectile function by inhibiting the AKT/eNOS signaling pathway.
低雄激素状态抑制勃起功能的机制尚未阐明。神经颗粒蛋白（Ng）是一种 Ca2+敏感的钙调蛋白结合蛋白，在血管内皮细胞中表达，调节 eNOS 功能。
探讨低雄激素状态是否通过调节阴茎海绵体组织中的 Ng/CaN/AKT/eNOS 通路抑制大鼠的勃起功能。
36 只 8 周龄雄性 Sprague-Dawley 大鼠随机分为 6 组（n=6）：4 周对照组（4w-control）、4 周去势组（4w-cast）、4 周去势+睾酮替代组（4w-cast+T）、8 周对照组（8w-control）、8 周去势组（8w-cast）和 8 周去势+睾酮替代组（8w-cast+T）。手术后 4 周和 8 周，检测最大阴茎海绵体内压/平均动脉压（ICPmax/MAP）比值。测定各组阴茎海绵体组织中 NO 水平及 Ng、钙调神经磷酸酶（CaN）、AKT、p-AKT（S473）、eNOS、p-eNOS（Ser1177）的表达。
Ng 和 CaN 主要表达于大鼠阴茎海绵体组织内皮细胞和平滑肌细胞的膜和细胞质中。去势组的 ICPmax/MAP 和 NO 浓度明显低于对照组和去势+T 替代组（p<0.01）。去势组大鼠阴茎海绵体组织 Ng 表达及 p-AKT/AKT、p-eNOS/eNOS 比值明显低于对照组和去势+T 替代组（p<0.01）。去势组大鼠阴茎海绵体组织 CaN 表达明显高于对照组和去势+T 替代组（p<0.01）。
抑制 Ng 的表达，继而通过抑制 AKT/eNOS 信号通路上调大鼠阴茎海绵体组织中 CaN 的表达，是低雄激素状态抑制勃起功能的上游机制之一。
