Xie Guo-Ping, Xia Ji-Yi, Liu Jun, Jiang Rui
Department of Urology,The Affiliated Hospital of Southwest University of Medicine, Luzhou, Sichuan 646000, China.
Central Laboratory, The Affiliated Hospital of Southwest University of Medicine, Luzhou, Sichuan 646000, China.
Zhonghua Nan Ke Xue. 2017 Jan;23(1):11-20.
To investigate whether androgens can regulate the expression of eNOS in rat corpus cavernosum through AKT3, PIK3CA, CALM, and CAV1 and influence erectile function.
Thirty-six 8-week-old male SD rats were randomly divided into groups A (4-week control), B (6-week control), C (4-week castration), D (6-week castration), E (4-week castration + testosterone replacement), and F (6-week castration + testosterone replacement). Both the testis and epididymis were removed from the rats in groups C, D, E and F, and on the second day after surgery, the animals of groups E and F were subcutaneously injected with testosterone propionate at 3 mg per kg of the body weight qd alt while all the others with isodose oil instead. At 4 weeks (for groups A, C and E) and 6 weeks (for groups B, D and F) after treatment, we detected the maximum intracavernous pressure (ICPmax), the mean carotid arterial pressure (MAP) and their ratio (ICPmax/MAP), measured the level of serum testosterone (T), and determined the expressions of eNOS, P-eNOS, AKT3, PIK3CA, CALM and CAV1 in the corpus cavernosum by Western blot and immunohistochemistry.
No statistically significant differences were observed in the body weight and MAP among different groups. The serum T level and ICPmax/MAP were remarkably lower in groups C and D than in the other four groups (P<0.01) as well as in groups E and F than in A and B (P<0.05) but exhibited no significant differences either between E and F or between A and B. Immunohistochemistry showed that eNOS and P-eNOS were mainly expressed in the vascular endothelial cell membrane and cavernous vascular lumen, while AKT3, PIK3CA, CALM and CAV1 chiefly in the vascular endothelial cell cytoplasm and membrane, with a few in the smooth muscle cells. Western blot analysis manifested that the expressions of eNOS, P-eNOS, AKT3, PIK3CA, CALM and CAV1 were markedly lower in groups C and D than in A, B, E and F (P<0.01) as well as in D than in C (P<0.05) but those in groups E and F did not showed any significant difference from those in A and B, nor E from F or A from B.
Androgens can improve erectile function by upregulating the expressions of AKT3, PIK3CA, CALM and CAV1 protein molecules and activating eNOS after its phosphorylation, though the exact molecular mechanisms are yet to be further studied.
探讨雄激素是否能通过AKT3、PIK3CA、CALM和CAV1调节大鼠阴茎海绵体中eNOS的表达并影响勃起功能。
将36只8周龄雄性SD大鼠随机分为A组（4周对照组）、B组（6周对照组）、C组（4周去势组）、D组（6周去势组）、E组（4周去势+睾酮替代组）和F组（6周去势+睾酮替代组）。对C、D、E和F组大鼠切除睾丸和附睾，术后第二天，E组和F组动物皮下注射丙酸睾酮，剂量为3mg/kg体重，每日一次，其余组注射等剂量油剂。治疗4周（A、C和E组）和6周（B、D和F组）后，检测阴茎海绵体内最大压力（ICPmax）、平均颈动脉压（MAP）及其比值（ICPmax/MAP），测定血清睾酮（T）水平，并通过蛋白质免疫印迹法和免疫组织化学法检测阴茎海绵体中eNOS、磷酸化eNOS、AKT3、PIK3CA、CALM和CAV1的表达。
不同组间体重和MAP无统计学显著差异。C组和D组的血清T水平和ICPmax/MAP显著低于其他四组（P<0.01），E组和F组低于A组和B组（P<0.05），但E组和F组之间以及A组和B组之间无显著差异。免疫组织化学显示，eNOS和磷酸化eNOS主要表达于血管内皮细胞膜和海绵体血管腔，而AKT3、PIK3CA、CALM和CAV1主要表达于血管内皮细胞质和膜，少数表达于平滑肌细胞。蛋白质免疫印迹分析表明，C组和D组中eNOS、磷酸化eNOS、AKT3、PIK3CA、CALM和CAV1的表达显著低于A、B、E和F组（P<0.01），D组低于C组（P<0.05），但E组和F组与A组和B组相比无显著差异，E组与F组、A组与B组之间也无显著差异。
雄激素可通过上调AKT3、PIK3CA、CALM和CAV1蛋白分子的表达并在eNOS磷酸化后激活eNOS来改善勃起功能，但其确切分子机制尚待进一步研究。
