Low androgen status inhibits erectile function by up‐regulating the expression of P2X receptors in rat corpus cavernosum

Guo, Caixia; Jiang, Jun; Cheng, Bo; Xie, Linlin; Lin, Haocheng; Jiang, Rui

doi:10.1111/and.13627

Cited by 5 publications

(8 citation statements)

References 28 publications

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“…Previous studies reported that the upregulation of ROCK in the corpus cavernosum of castrated rats, diabetes rats, cavernous nerve injury rats, and spontaneously hypertensive rats could cause fibrosis and transdifferentiation of SMCs into myoblasts, resulting in cavernous fibrosis and eventually inhibited erectile function. 8 , 42-48 Furthermore, the decrease in galanin and GalR1-3 levels resulted in decreases in p-eNOS/eNOS, NO synthesis and release, and ICPmax/MAP. 8 , 42-46 Testosterone replacement resulted in significant upregulation of galanin and GalR1-3, a decrease of ROCK1 and ROCK2 protein expression in rat penile tissue, an increase of p-eNOS/eNOS and NO release, and eventual improvement of ICPmax/MAP in castrated rats.…”

Section: Discussionmentioning

confidence: 96%

“… 8 , 42-48 Furthermore, the decrease in galanin and GalR1-3 levels resulted in decreases in p-eNOS/eNOS, NO synthesis and release, and ICPmax/MAP. 8 , 42-46 Testosterone replacement resulted in significant upregulation of galanin and GalR1-3, a decrease of ROCK1 and ROCK2 protein expression in rat penile tissue, an increase of p-eNOS/eNOS and NO release, and eventual improvement of ICPmax/MAP in castrated rats. Some studies found that crosstalk between the RhoA/ROCK signaling pathway and eNOS/NO signaling pathway is involved in the inhibition of eNOS phosphorylation.…”

Section: Discussionmentioning

confidence: 96%

“…Supplementation of testosterone increased p-eNOS/eNOS and the content of SMCs and ECs, resulting in enhancing the erection of castrated rats. 7 , 8 However, for patients who need to maintain low androgen status, such as those with prostate cancer, it is very important to find ways to ameliorate their erectile function.…”

Section: Introductionmentioning

confidence: 99%

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Downregulation of the expression of galanin impairs erectile function in hypoandrogenic rats

Yuan

Xiong

et al. 2023

Sexual Medicine

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Background The relationship between galanin and erectile function under low androgen levels is still unclear. Aim To explore whether a low testosterone level damages the erection of a rat by regulating the expression of galanin and GalR in penile cavernous tissue. Methods Thirty-six male Sprague-Dawley rats, 8 weeks of age, were randomly grouped as follows (n = 6): control, castration, castration + testosterone replacement, control + transfection, castration + transfection, and castration + empty transfection. At 4 weeks after castration, rats in the transfection group were injected with lentivirus carrying the targeting galanin gene (2 × 108 TU/mL, 10 μL) in the corpus cavernosum. After 1 week of injection, the intracavernosal pressure (ICP), mean arterial blood pressure (MAP), nitric oxide (NO), serum testosterone concentration, galanin, GalR1-3, ROCK1, ROCK2, and p-eNOS/eNOS in the rat penile tissues were evaluated. Outcomes ICPmax/MAP and the expression of galanin in the corpus cavernosum in castrated rats were obviously decreased as compared with those in the control rats. Results The castrated rats showed remarkably lower ICPmax/MAP, galanin, GalR1-3, p-eNOS/eNOS, and NO content and markedly higher ROCK1 and ROCK2 in penile tissues than the control group (P < .05). The transfected rats administrated with LV Gal had obviously higher ICPmax/MAP, p-eNOS/eNOS, and NO content and less ROCK1 and ROCK2 protein expression in the corpus cavernosum when compared with the castration group (P < .05). Clinical Translation Upregulating the expression of galanin in the penile corpus cavernosum might be a novel method of treating erectile dysfunction caused by a low androgen level. Strengths and Limitations The conclusions obtained in the animal experiments need to be confirmed in human data. Conclusion The erectile function of hypoandrogen rats might be inhibited by downregulating the level of galanin and GalR1-3, upregulating ROCK1 and ROCK2 levels, and inhibiting the eNOS/NO signaling pathway in penile corpus cavernosum.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 96%

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Downregulation of the expression of galanin impairs erectile function in hypoandrogenic rats

Yuan

Xiong

et al. 2023

Sexual Medicine

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“…RhoA/Rho‐kinase is an important signalling pathway that regulates SMC contraction during penile erection. Our previous study found that the RhoA/Rho kinase signalling pathway was activated by the upregulation of P2X1, P2X2 and P2X3 expression in rat penile cavernous tissue under low androgen levels, resulting in the impaired erectile function (Guo et al, 2020). However, whether other mechanisms are involved in regulating RhoA/Rho‐kinase is unclear.…”

Section: Discussionmentioning

confidence: 99%

Effect of low androgen levels on transient receptor potential channels expression in rat penile corpus cavernosum tissue and its relationship with erectile function

Zhu

Liu

et al. 2022

Andrologia

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The exact mechanism by which testosterone deficiency causes ED has not yet been elucidated. TRPC is involved in the process of smooth muscle cell contraction and relaxation. The effect of androgens on TRPCs and their relationship with erectile function are currently unclear. Thirty male SD rats were randomly divided into six groups: control group, castration group, castration + testosterone (T) group (cast + T), control + transfection group (control + trans), control + empty transfection group and castration + transfection group (cast + trans). The transfection group rats were given with lentivirus (1 Â 10 8 TU/mL, 15 μl) carrying the siRNA targeting TRPC4 gene in the rat penile cavernous tissue at 4 weeks after castration. The tests were performed at 5 weeks after castration. Comparing the cast group with the control, the ICPmax/MAP, p-eNOS/eNOS and NO levels in the rat penile tissue were significantly lower (p < 0.01) and the level of TRPC3, TRPC4 and TRPC6 in the rat penile tissue was significantly increased (p < 0.01). When the cast + trans group was compared to the cast group, ICPmax/MAP was markedly higher (p < 0.05), and the level of the TRPC4 was remarkably lower (p < 0.05). Low androgen levels might inhibit an erectile function through up-regulation of the expression of TRPC3, TRPC4 and TRPC6 in rat penile cavernous tissue. Inhibition the level of TRPC4 in rat penile tissue may improve the erectile function in low androgen levels.

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“…The rat penile cavernous tissues were cut into three sections and stored at −80 °C until the determination of NO and RhoA-GTP and western blotting. The other two parts of the penis were used for immunohistochemistry (IHC) and immunofluorescence examination ( 7 ).…”

Section: Methodsmentioning

confidence: 99%

A low androgen state impairs erectile function by suppressing EPAC1 in rat penile corpus cavernosum

Lin,

Long,

Liu

et al. 2023

Transl Androl Urol

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Background Exchange proteins activated by cAMP 1 ( EPAC1 ) can promote vasodilatation by regulating endothelial nitric oxide synthase (eNOS) activity through the phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) pathway and prevent vascular smooth muscle contraction by restraining the ras homolog gene family, member A/Rho-associated coiled-coil forming protein kinase (RhoA/ROCK) pathway. However, the relationship among EPAC1 , androgen and erectile function is still unknown. Therefore, we attempted to investigate whether EPAC1 expresses in penile corpus cavernosum of rats and how EPAC1 affects erectile function under low androgenic conditions. Methods Thirty 8-week-old Sprague-Dawley male rats were randomly divided into six groups (n=5): sham operation (sham), castrated, castrated + testosterone replacement (castrated + T), sham + EPAC1 over-expression lentivirus (sham + EPAC1 ), castrated + empty lentivirus vector (castrated + empty vector), and castrated + EPAC1 . Four weeks after the operation, the lentivirus vectors carrying the EPAC1 gene were injected into the penile corpus cavernosum of the sham + EPAC1 and castrated + EPAC1 groups (1×10 8 TU/mL, 20 µL per rat). A week after injection, the ratio of maximum intracavernous pressure to mean arterial pressure (ICPmax/MAP) and the levels of serum testosterone (T), nitric oxide (NO), the active form of RhoA (RhoA-GTP), AKT, phospho-AKT (p-AKT), eNOS, phospho-eNOS (p-eNOS), p-AKT/AKT, p-eNOS/eNOS and EPAC1 levels were measured. Results In comparison to the sham group, ICPmax/MAP and EPAC1 content in the castrated group were significantly reduced. EPAC1 is primarily located in the cyto-membrane and cytoplasm of endothelial cells and smooth muscle cells in the rat penile corpus cavernosum. In comparison to the sham group, the T, ICPmax/MAP and NO levels of the castrated group were significantly reduced (P<0.01). Meanwhile, the RhoA-GTP concentration in the castrated + EPAC1 group was reduced in comparison with the castrated + empty vector group (P<0.01). Compared with the castrated + empty vector group, the p-AKT/AKT, EPAC1 and p-eNOS/eNOS levels in the castrated + EPAC1 group were significantly increased (P<0.05). Conclusions Androgen deficiency can suppress EPAC1 expression in the penile corpus cavernosum of rats, while the up-regulation of which can improve the erectile function of castrated rats.

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Low androgen status inhibits erectile function by up‐regulating the expression of P2X receptors in rat corpus cavernosum

Cited by 5 publications

References 28 publications

Downregulation of the expression of galanin impairs erectile function in hypoandrogenic rats

Downregulation of the expression of galanin impairs erectile function in hypoandrogenic rats

Effect of low androgen levels on transient receptor potential channels expression in rat penile corpus cavernosum tissue and its relationship with erectile function

A low androgen state impairs erectile function by suppressing EPAC1 in rat penile corpus cavernosum

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