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Higher expression of phosphodiesterase type 5 in the anterior fibromuscular stroma of the human prostate

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Abstract

Purpose

To examine phosphodiesterase type 5 (PDE5) expression in the anterior fibromuscular stroma (AFMS) of the prostate. Although PDE5 expression was identified in the human prostate, differences in PDE5 expression in intra-prostatic regions are unknown. The AFMS in the prostate has peculiar innervations that could contribute to voiding function. Here, we examined regional differences in PDE5 expression in the prostate with special reference to the AFMS.

Methods

A total 18 human prostate and bladder specimens were obtained. Tissue specimens were processed by hematoxylin–eosin (H&E) staining and immunohistochemistry for PDE5. Immunoreactivity with PDE5 was evaluated using computer-assisted image analysis in the following regions: the AFMS, bladder neck, stromal hyperplasia in the transition zone, glandular hyperplasia in the transition zone (TZ gland), and the peripheral zone (PZ). The correlation between PDE5 expression in the AFMS and clinical data was analysed.

Results

Image analysis revealed that the median ratio of the PDE5-immunoreactive area to smooth muscle area by H&E staining was 74.7% in the AFMS. There was significantly higher PDE5 expression in the AFMS than in the TZ gland (p = 0.034) and PZ (p = 0.002). PDE5 expression in the AFMS was not significantly correlated with age, prostate volume, transition zone volume, or transition zone index. However, older men had a tendency to have higher PDE5 expression in the AFMS.

Conclusions

We found higher PDE5 expression in the AFMS compared with other prostatic regions, which suggested that the AFMS is a target region of PDE5 inhibitors in the prostate.

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Fig. 1

(modified from Ref. [11])

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References

  1. Gacci M, Eardley I, Giuliano F, Hatzichristou D, Kaplan SA, Maggi M, McVary KT, Mirone V, Porst H, Roehrborn CG (2011) Critical analysis of the relationship between sexual dysfunctions and lower urinary tract symptoms due to benign prostatic hyperplasia. Eur Urol 60(4):809–825

    Article  Google Scholar 

  2. Lue TF, Giuliano F, Montorsi F, Rosen RC, Andersson KE, Althof S, Christ G, Hatzichristou D, Hirsh M, Kimoto M, Lewis R, Mckenna K, MacMahon C, Morales A, Mulcahy J, Padma-Nathan H, Pryor J, de Tejada IS, Shabsigh R, Wagner G (2004) Summary of the recommendations on sexual dysfunctions in men. J Sex Med 1(1):6–23

    Article  Google Scholar 

  3. McVary KT, Monnig W, Camps JL Jr, Young JM, Tseng LJ, van den Ende G (2007) Sildenafil citrate improves erectile function and urinary symptoms in men with erectile dysfunction and lower urinary tract symptoms associated with benign prostatic hyperplasia: a randomized, double-blind trial. J Urol 177(3):1071–1077

    Article  CAS  Google Scholar 

  4. Stacey P, Rulten S, Dapling A, Phillips SC (1998) Molecular cloning and expression of human cGMP-binding cGMP-specific phosphodiesterase (PDE5). Biochem Biophys Res Commun 247(2):249–254

    Article  CAS  Google Scholar 

  5. Morelli A, Filippi S, Mancina R, Luconi M, Vignozzi L, Marini M, Orlando C, Vannneli GB, Aversa A, Natali A, Forti G, Giogi M, Jannini EA, Ledda F, Maggi M (2004) Androgens regulate phosphodiesterase type 5 expression and functional activity in corpora cavernosa. Endocrinology 145(5):2253–2263

    Article  CAS  Google Scholar 

  6. Ückert S, Kuthe A, Jonas U, Stief CG (2001) Characterization and functional relevance of cyclic nucleotide phosphodiesterase isoenzymes of the human prostate. J Urol 166(6):2484–2490

    Article  Google Scholar 

  7. Filippi S, Morelli A, Sandner P et al (2007) Characterization and functional role of androgen-dependent PDE5 activity in the bladder. Endocrinology 148:1019–1029

    Article  CAS  Google Scholar 

  8. Ückert S, Oelke M, Stief CG et al (2006) Immunohistochemical distribution of cAMP- and cGMP-phosphodiesterase (PDE) isoenzymes in the human prostate. Eur Urol 49:740–745

    Article  Google Scholar 

  9. Zenzmaier C, Sampson N, Pernkopf D, Plas E, Untergasser G, Berger P (2010) Attenuated proliferation and trans-differentiation of prostatic stromal cells indicate suitability of phosphodiesterase type 5 inhibitors for prevention and treatment of benign prostatic hyperplasia. Endocrinology 151(8):3975–3984

    Article  CAS  Google Scholar 

  10. McNeal JE (1972) The prostate and prostatic urethra: a morphologic synthesis. J Urol 107(6):1008–1016

    Article  CAS  Google Scholar 

  11. McNeal JE (1978) Origin and evolution of benign prostatic enlargement. Investig Urol 15:340–345

    CAS  Google Scholar 

  12. Iwata T, Ukimura O, Inaba M, Kojima M, Kumamoto K, Ozawa H, Kawata M, Miki T (2001) Immunohistochemical studies on the distribution of nerve fibers in the human prostate with special reference to the anterior fibromuscular stroma. Prostate 48(4):242–247

    Article  CAS  Google Scholar 

  13. Ukimura O, Iwata T, Ushijima S, Suzuki K, Honjo H, Okihara K, Mizutani Y, Kawauchi A, Miki T (2004) Possible contribution of prostatic anterior fibromuscular stroma to age-related urinary disturbance in reference to pressure-flow study. Ultrasound Med Biol 30(5):575–581

    Article  Google Scholar 

  14. Ehrlich Y, Foster RS, Bihrle R, Cheng L, Tong Y, Koch MO (2010) Division of prostatic anterior fibromuscular stroma reduces urethral resistance in an ex vivo human prostate model. Urology 76(2):511 e10–3

  15. Nishio K, Soh S, Syukuya T, Sato R, Sadaoka Y, Iwahata T, Suzuki K, Ashizawa Y, Kobori Y, Okada H (2014) Role of male pelvic floor muscles and anterior fibromuscular stroma in males on alpha(1)-blocker treatment: a magnetic resonance imaging study. Int J Urol 21(7):724–727

    Article  Google Scholar 

  16. Kotera J, Fujishige K, Omori K (2000) Immunohistochemical Localization of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in rat tissues. J Histochem Cytochem 48(5):685–693

    Article  CAS  Google Scholar 

  17. Kaplan SA, Te AE, Pressler LB, Olsson CA (1995) Transition zone index as a method of assessing benign prostatic hyperplasia: correlation with symptoms, urine flow and detrusor pressure. J. Urol 154:1764–1769

    Article  CAS  Google Scholar 

  18. Zhang W, Zang N, Jiang Y, Chen P, Wang X, Zhang X (2015) Upregulation of phosphodiesterase type 5 in the hyperplastic prostate. Sci Rep 5:17888

    Article  CAS  Google Scholar 

  19. Zhao C, Kim SH, Lee SW et al (2011) Activity of phosphodiesterase type 5 inhibitors in patients with lower urinary tract symptoms due to benign prostatic hyperplasia. BJU Int 107:1943–1947

    Article  Google Scholar 

  20. Ückert S, Waldkirch ES, Merseburger AS et al (2013) Phosphodiesterase type 5 (PDE5) is co-localized with key proteins of the nitric oxide/cyclic GMP signaling in the human prostate. World J Urol 31:609–614

    Article  Google Scholar 

  21. Giuliano F, Ückert S, Maggi M et al (2013) The mechanism of action of phosphodiesterase type 5 (PDE5) inhibitors in the treatment of lower urinary tract symptoms related to benign prostatic hyperplasia. Eur Urol 63:506–516

    Article  CAS  Google Scholar 

  22. Fibbi B, Morelli A, Vignozzi L et al (2010) Characterization of phosphodiesterase type 5 expression and functional activity in the human male lower urinary tract. J Sex Med 7(1):59–69

    Article  CAS  Google Scholar 

  23. Gacci M, Corona G, Vignozzi L, Salvi M, Serni S, De Nunzio C, Tubaro A, Oelke M, Carini M, Maggi M (2015) Metabolic syndrome and benign prostatic enlargement: a systematic review and meta-analysis. BJU Int 115(1):24–31

    Article  Google Scholar 

  24. Vignozzi L, Gacci M, Cellai I, Morelli A, Maneschi E, Comeglio P, Santi R, Filippi S, Sebastianelli A, Nesi G, Serni S, Carini M, Maggi M (2013) PDE5 inhibitors blunt inflammation in human BPH: a potential mechanism of action for PDE5 inhibitors in LUTS. Prostate 73(13):1391–1402

    Article  CAS  Google Scholar 

  25. Morelli A, Comeglio P, Filippi S, Sarchielli E, Vignozzi L, Maneschi E, Cellai I, Gacci M, Lenzi A, Vannelli GB, Maggi M (2013) Mechanism of action of phosphodiesterase type 5 inhibition in metabolic syndrome-associated prostate alterations: an experimental study in the rabbit. Prostate 73(4):428–441

    Article  CAS  Google Scholar 

  26. Iwata T, Ukimura O, Kojima M, Ozawa H, Kawata M, Miki T (1999) Age-related increase of the connective tissue in the anterior fibromuscular stroma of the prostate. Neurourol Urodyn 18(4):360

    Google Scholar 

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Funding

This research was funded by GlaxoSmithKline (GSK) Japan Research Grant 2016 (No. D14)

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Authors and Affiliations

  1. Department of Urology, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kyoto, 602-8566, Japan

    Tsuyoshi Iwata, Atsuko Fujihara, Takumi Shiraishi, Yasuhiro Yamada, Fumiya Hongo & Osamu Ukimura

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  1. Tsuyoshi Iwata
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  2. Atsuko Fujihara
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  3. Takumi Shiraishi
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  4. Yasuhiro Yamada
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  5. Fumiya Hongo
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  6. Osamu Ukimura
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Correspondence to Tsuyoshi Iwata.

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Iwata, T., Fujihara, A., Shiraishi, T. et al. Higher expression of phosphodiesterase type 5 in the anterior fibromuscular stroma of the human prostate. World J Urol 38, 2915–2921 (2020). https://doi.org/10.1007/s00345-020-03095-1

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  • DOI: https://doi.org/10.1007/s00345-020-03095-1

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