Article | Published:

The effects of testosterone replacement on penile structure and erectile function after long-term castration in adult male rats

International Journal of Impotence Researchvolume 30pages122128 (2018) | Download Citation

Abstract

Short periods of testosterone suppression have been shown to reduce trabecular smooth muscle content and increase interstitial connective tissue accumulation in animal models. However, the long-term effects of testosterone suppression remain unclear. The aim of this study was to evaluate the long-term effects of testosterone suppression on penile structure and erectile function in rats. Subjects were divided into two groups by observation period (short-period group (group I), 12 weeks; long-period group (group II), 20 weeks). Each group comprised three different subgroups (10 rats each): sham-operated control, surgical castration, and testosterone replacement (4 weeks after an 8-week castration period). Group II subgroups included a sham control, surgical castration, and testosterone replacement (4 weeks after a 16-week castration period). Erectile function was assessed by measuring intracavernosal pressure in response to cavernous nerve stimulation, and expression of the endothelial nitric oxide synthase (eNOS) protein was determined by western blot analysis. Serum testosterone values were measured via radioimmunoassay. The results indicated that serum testosterone level, penile length and girth, cavernosal smooth muscle content, and eNOS activity decreased significantly in castrated animals. These effects were rescued by testosterone undecanoate injection. Erectile function was normalized over 4 weeks in rats that received androgen replacement. Expression of eNOS was decreased in the corpus cavernosum of castrated animals compared with controls, while androgen replacement normalized the expression of eNOS. These results were consistently observed regardless of the duration of androgen deprivation. Thus, these data suggest that androgen regulates the expression of eNOS in the rat penile corpus cavernosum and confirm the importance of androgens in the maintenance of erectile function. Additionally, long-term androgen deprivation does not induce irreversible structural or erectile functional changes in sexually mature adult male rats.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1.

    Traish AM. Androgens play a pivotal role in maintaining penile tissue architecture and erection: a review. J Androl 2009;30:363–9.

  2. 2.

    Park KKK, Lee SHS, Chung BHB. The effects of long-term androgen deprivation therapy on penile length in patients with prostate cancer: a single-center, prospective, open-label, observational study. J Sex Med 2011;8:3214–9.

  3. 3.

    Traish AM, Park K, Dhir V, Kim NN, Moreland RB, Goldstein I. Effects of castration and androgen replacement on erectile function in a rabbit model. Endocrinology 1999;140:1861–8.

  4. 4.

    Traish A, Munarriz R, O’Connell L, Choi S, Kim S Effects of medical or surgical castration on erectile function in an animal model. J Androl 2003;24:381–384

  5. 5.

    Lu Y-L, Kuang L, Zhu H, Wu H, Wang X-F, Pang Y-P, et al Changes in aortic endothelium ultrastructure in male rats following castration, replacement with testosterone and administration of 5alpha-reductase inhibitor. Asian J Androl 2007;9:843–7.

  6. 6.

    Keast JR, Gleeson RJ, Shulkes A, Morris MJ. Maturational and maintenance effects of testosterone on terminal axon density and neuropeptide expression in the rat vas deferens. Neuroscience 2002;112:391–8.

  7. 7.

    Hwang EC, Oh KJ, Jung SI, Kim NN, Ahn KY, Park K. Effects of androgen on the expression of vascular endothelial growth factor in the penile corpus cavernosum. Urology 2011;77:1381–1386

  8. 8.

    Traish A, Kim N. The physiological role of androgens in penile erection: regulation of corpus cavernosum structure and function. J Sex Med 2005;2:759–70.

  9. 9.

    Miranda AF, Gallo CB, De Souza DB, Costa WS, Sampaio FJ. Effects of castration and late hormonal replacement in the structure of rat corpora cavernosa. J Androl 2012;33:1224–1232

  10. 10.

    Vasconcelos JS, Figueiredo RT, Nascimento FLB, Damião R, da Silva EA. The natural history of penile length after radical prostatectomy: a long-term prospective study. Urology 2012;80:1293–7.

  11. 11.

    Fraiman M, Lepor H, McCullough A. Changes in penile morphometrics in men with erectile dysfunction after nerve-sparing radical retropubic prostatectomy. Mol Urol 1999;3:109–15.

  12. 12.

    Munding MD, Wessells HB, Dalkin BL. Pilot study of changes in stretched penile length 3 months after radical retropubic prostatectomy. Urology 2001;58:567–569

  13. 13.

    Haliloglu A, Baltaci S, Yaman O. Penile length changes in men treated with androgen suppression plus radiation therapy for local or locally advanced prostate cancer. J Urol 2007;177:128–30.

  14. 14.

    Traish AM, Guay AT. Are androgens critical for penile erections in humans? Examining the clinical and preclinical evidence. J Sex Med 2006;3:382–407.

  15. 15.

    Ory J, Flannigan R, Lundeen C, Huang JG, Pommerville P, Goldenberg SL. Testosterone therapy in patients with treated and untreated prostate cancer: impact on oncologic outcomes. J Urol 2016;196:1082–9.

Download references

Acknowledgements

This work was supported by the research grant of the Jeju National University Hospital in 2014. * Jung Sik Huh and Byung Ha Chung, both author equally contributed to complete this study as first author

Author information

Author notes

  1. These authors contributed equally and are joint first authors: Jung Sik Huh and Byung Ha Chung.

Affiliations

  1. Department of Urology, Jeju National University Hospital, Jeju National University, Jeju, South Korea

    • Jung Sik Huh
    •  & Kyung Kgi Park
  2. Department of Urology, Gangnam Severance Hospital, Yonsei University Health system, Seoul, South Korea

    • Byung Ha Chung
    •  & Chang Hee Hong
  3. Department of Urology, Inha University School of medicine, Incheon, South Korea

    • Ji Kan Ryu
  4. Department of Urology, Severance Hospital, Yonsei University Health System, Seoul, South Korea

    • Jang Hwan Kim
    •  & Woong Kyu Han

Authors

  1. Search for Jung Sik Huh in:

  2. Search for Byung Ha Chung in:

  3. Search for Chang Hee Hong in:

  4. Search for Ji Kan Ryu in:

  5. Search for Jang Hwan Kim in:

  6. Search for Woong Kyu Han in:

  7. Search for Kyung Kgi Park in:

Conflict of interest

The authors declare that they have no competing interests.

Corresponding author

Correspondence to Kyung Kgi Park.

About this article

Publication history

Received

Revised

Accepted

Published

DOI

https://doi.org/10.1038/s41443-017-0010-6