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Testosterone improved erectile function by upregulating transcriptional expression of growth factors in late androgen replacement therapy model rats

Abstract

We previously showed that castration of rats reduced erectile function over time; when testosterone replacement therapy was started 4 weeks after castration, erectile function improved. In this study, we examined the mechanism of improvement in erectile function following testosterone replacement therapy in rats. Thirty 12-week-old rats were divided into castrated (Cast), castrated with subcutaneous administration of testosterone (Cast + T), and sham (Sham) groups. Erectile function and mRNA and protein expression were evaluated in the rats by using standard methods. To assess erectile function, we measured the intracavernosal pressure, mean arterial pressure, mRNA expression of endothelial growth factors, and protein expression of endothelial nitric oxide synthase (eNOS). The intracavernosal pressure/mean arterial pressure ratio was significantly lower in the Cast group, and testosterone administration significantly improved (P = 0.017). Compared to the Cast group, the Cast+T group exhibited significantly increased mRNA expressions of vascular endothelial growth factor A (VEGF-A), intercellular adhesion molecule 1 (ICAM-1), transforming growth factor-β (TGF-β), nerve growth factor (NGF), α-smooth muscle actin (α-SMA), caveolae associated protein 1 (Cavin-1), Cavin-2, Cavin-3, sirtuin 1 (Sirt-1), sphingosine-1-phosphate 1 (S1P1), S1P2, and S1P3 and eNOS protein expression. Testosterone replacement therapy improved erectile function in castrated rats by increasing growth factors and eNOS protein.

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Fig. 1: Treatment protocols and teststerone levels.
Fig. 2: Erectile function evaluation.
Fig. 3: Expression of mRNA in the corpus cavernosum of rats.
Fig. 4: Western blot analysis of the expression of nitric oxide synthase in the corpus cavernosum of Sham, Cast and Cast+T rats. Representative immunoblots of eNOS.
Fig. 5

Data availability

The datasets generated during and analysed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We acknowledge the assistance of the Research Equipment Sharing Center at the Nagoya City University.

Funding

This work was supported in part by Grants-in-Aid for Scientific Research (KAKENHI, 20K09563) from the Japan Society for the Promotion of Science (JSPS) and the 24th General Assembly of the Japanese Association of Medical Sciences.

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Conceptualization, TK and KK; Data curation, TK, IH, TM, YH, and YM; Formal analysis, TK and IH.; Funding acquisition, TK, YH, and KK; Investigation, TK, IH, and TM; Methodology, TK and YH; Project administration, TK; Supervision, YH, AS, YM, YFH, and KK; Writing-original draft, TK and KK; Writing-review & editing TK and KK.

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Correspondence to Tomoya Kataoka or Kazunori Kimura.

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Kataoka, T., Ito, H., Mori, T. et al. Testosterone improved erectile function by upregulating transcriptional expression of growth factors in late androgen replacement therapy model rats. Int J Impot Res (2022). https://doi.org/10.1038/s41443-022-00627-8

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