Low testosterone state inhibits erectile function by downregulating the expression of GIT1 in rat penile corpus cavernosum

JianBin Gu; Li-Kun Zhu; Xin Zhao; Jun Jiang; Rui Jiang

doi:10.1093/sexmed/qfad017

Low testosterone state inhibits erectile function by downregulating the expression of GIT1 in rat penile corpus cavernosum

Sex Med. 2023 May 29;11(2):qfad017. doi: 10.1093/sexmed/qfad017. eCollection 2023 Apr.

Authors

JianBin Gu¹, Li-Kun Zhu¹, Xin Zhao¹, Jun Jiang², Rui Jiang^{1

3}

Affiliations

¹ Department of Urology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
² Department of Thyroid Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
³ Department of Urology, Nephropathy Clinical Medical Research Center of Sichuan Province, Luzhou, 646000, China.

Abstract

Background: The mechanism of erectile dysfunction (ED) caused by a low androgen level is still not clear.

Aim: To explore the influence of the low testosterone state on G protein-coupled receptor kinase interactor 1 (GIT1) and its contact to erectile function.

Methods: 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 GIT1 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.

Outcomes: The levels of GIT1 in the penile cavernous tissue of castrated rats are significantly lower than that of controls.

Results: 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 (P < .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 (P < .01).

Clinical translation: Modulating the interaction between eNOS and GIT1 might be a novel method of treating ED caused by a low androgen level.

Strengths and limitations: The impact of GIT1 phosphorylation on the activity of eNOS and its possible mechanisms affecting erectile function require further study.

Conclusion: A low testosterone state inhibits erectile function in rats by reducing the expression of GIT1 and the protein interaction between GIT1 and eNOS.

Keywords: G protein–coupled receptor kinase interactor 1 (GIT1); androgen; hypoandrogenism; nitric oxide synthase; protein-protein interaction.