Gu JianBin, Zhu Li-Kun, Zhao Xin, Jiang Jun, Jiang Rui
Department of Urology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
Department of Thyroid Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
Sex Med. 2023 May 29;11(2):qfad017. doi: 10.1093/sexmed/qfad017. eCollection 2023 Apr.
The mechanism of erectile dysfunction (ED) caused by a low androgen level is still not clear.
To explore the influence of the low testosterone state on G protein-coupled receptor kinase interactor 1 (GIT1) and its contact to erectile function.
Thirty male Sprague-Dawley rats aged 8 weeks were distributed at random into 5 groups: control (sham operated), castration, testosterone supplement after castration, castration + vacant lentiviral transfection, and castration + lentiviral transfection. The testis and epididymis were removed through a scrotal incision to develop castrated rats. Four weeks after castration, a lentivirus carrying the gene was injected into the middle of rat penile corpus cavernosum. One week after transfection, maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP), serum testosterone, nitric oxide, GIT1, endothelial nitric oxide synthase (eNOS), phospho-eNOS (p-eNOS), p-eNOS/eNOS, and the interaction between eNOS and GIT1 were assessed in the rats.
The levels of GIT1 in the penile cavernous tissue of castrated rats are significantly lower than that of controls.
GIT1 was expressed in the cytoplasm and cell membrane of vascular endothelial cells and smooth muscle cells in rat penile tissue. In comparison with normal rats, the castrated rats showed lower levels of GIT1 expression, GIT1 and eNOS interaction, p-eNOS/eNOS, nitric oxide, and ICPmax/MAP ( < .01). Overexpression of GIT1 can intensively enhance the expression level of GIT1, the interaction between GIT1 and eNOS, p-eNOS/eNOS, nitric oxide, and ICPmax/MAP in rats ( < .01).
Modulating the interaction between eNOS and GIT1 might be a novel method of treating ED caused by a low androgen level.
The impact of GIT1 phosphorylation on the activity of eNOS and its possible mechanisms affecting erectile function require further study.
A low testosterone state inhibits erectile function in rats by reducing the expression of GIT1 and the protein interaction between GIT1 and eNOS.
雄激素水平低下所致勃起功能障碍（ED）的机制尚不清楚。
探讨低睾酮状态对G蛋白偶联受体激酶相互作用蛋白1（GIT1）的影响及其与勃起功能的关系。
将30只8周龄雄性Sprague-Dawley大鼠随机分为5组：对照组（假手术）、去势组、去势后补充睾酮组、去势+空载体慢病毒转染组、去势+GIT1基因慢病毒转染组。通过阴囊切口切除睾丸和附睾制备去势大鼠模型。去势4周后，将携带GIT1基因的慢病毒注射到大鼠阴茎海绵体中部。转染1周后，检测大鼠海绵体内最大压力/平均动脉压（ICPmax/MAP）、血清睾酮、一氧化氮、GIT1、内皮型一氧化氮合酶（eNOS）、磷酸化eNOS（p-eNOS）、p-eNOS/eNOS以及eNOS与GIT1的相互作用。
去势大鼠阴茎海绵体组织中GIT1水平显著低于对照组。
GIT1表达于大鼠阴茎组织血管内皮细胞和平滑肌细胞的细胞质及细胞膜。与正常大鼠相比，去势大鼠GIT1表达水平、GIT1与eNOS相互作用、p-eNOS/eNOS、一氧化氮水平及ICPmax/MAP均降低（P<0.01）。过表达GIT1可显著提高大鼠GIT1表达水平、GIT1与eNOS相互作用、p-eNOS/eNOS、一氧化氮水平及ICPmax/MAP（P<0.01）。
调节eNOS与GIT1的相互作用可能是治疗雄激素水平低下所致ED的新方法。
GIT1磷酸化对eNOS活性的影响及其影响勃起功能的可能机制有待进一步研究。
低睾酮状态通过降低GIT1表达及GIT1与eNOS的蛋白相互作用抑制大鼠勃起功能。
