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. 2020 Mar;8(1):114-119.
doi: 10.1016/j.esxm.2019.10.003. Epub 2019 Nov 22.

Testosterone Induces Relaxation of Human Corpus Cavernosum Tissue of Patients With Erectile Dysfunction

Thomas Van den Broeck  1 , Mohammad Ayodhia Soebadi  2 , Annelies Falter  3 , Lore Raets  3 , Jolien Duponselle  3 , Joline Lootsma  3 , Alexander Heintz  3 , Uchelly Philtjens  3 , Lien Hofkens  3 , Arantxa Gonzalez-Viedma  3 , Karel Driesen  3 , Peter Sandner  4 , Maarten Albersen  5 , Bert Brône  6 , Koenraad Van Renterghem  7
Affiliations

Testosterone Induces Relaxation of Human Corpus Cavernosum Tissue of Patients With Erectile Dysfunction

Thomas Van den Broeck et al. Sex Med. 2020 Mar.

Abstract

Introduction: Previous research in the field of cardiovascular diseases suggests a relaxing effect of testosterone (T) on smooth muscle cells. Therefore, it was hypothesized that T could play a significant role in erection development.

Aim: To investigate the relaxing effect of T and other molecules of the T signaling pathway on human corpus cavernosum (HCC) tissue.

Methods: Samples of the HCC tissue were obtained from men who underwent penile prosthesis implantation (n = 33) for erectile dysfunction. Samples were used for isometric tension measurement in Ex Vivo experiments. Following standardized precontraction with phenylephrine, increasing doses of T or dihydrotestosterone were administered and blocked by NO/H2S synthesis inhibitors, a KATP blocker, and flutamide (androgen receptor inhibitor).

Main outcome measure: The outcome was relaxation of the HCC tissue, normalized to a maximum precontraction achieved by phenylephrine.

Results: A dose-dependent relaxing effect of dihydrotestosterone and T was observed with a relaxation of, respectively, 24.9% ± 23.4% (P < .0001) and 41.7% ± 19.1% (P = .01) compared with 6.8% ± 15.9% for vehicle (dimethylsulfoxide) at 300 μM. The relaxing effect of T was not countered by blocking NO synthesis, H2S synthesis, KATP channels, or the androgen receptor.

Clinical implications: By understanding the underlying mechanisms of T-induced HCC relaxation, potential new therapeutic targets can be identified.

Strengths & limitations: The strength of the study is the use of fresh HCC tissues with reproducible results. The limitation is the need for supraphysiological T levels to induce the observed effect.

Conclusion: Rapid androgen-induced relaxation of HCC is likely to occur via nongenomic mechanisms. Previously suggested mechanisms of action by which T modulates HCC relaxation have been excluded. Van den Broeck T, Soebadi MA, Falter A, et al. Testosterone Induces Relaxation of Human Corpus Cavernosum Tissue of Patients With Erectile Dysfunction. J Sex Med 2019; 8:114-119.

Keywords: Humans; In Vitro Techniques; Male; Muscle; Muscle Relaxation; Penis/Physiology; Smooth/Physiology; Testosterone/Physiology.

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Figures

Figure 1
Figure 1
Isometric tension measurement assay of human corpus cavernosum tissue. The Y-axis represents the relative decrease in tension of the tissue after maximal contraction induced by phenylephrine. Data are normalized to maximal pre-contraction ± SEM. DMSO and SNP, respectively, serve as the negative and positive control. T, testosterone; DHT, dihydrotestosterone; DMSO, dimethylsulfoxide; SNP, sodium nitroprusside; SEM, standard error of mean. Statistical analysis using two-way analysis of variance comparing the effect sizes of the reported drugs to DMSO. *P < .05, **P < .01, ***P < .001, ****P < .0001.
Figure 2
Figure 2
Isometric tension measurement assay of human corpus cavernosum tissue investigating the effect of (A) L-NAME, (B) PAG, (C) BCA, and (D) Glim on the relaxation induced by T. The Y-axis represents the relative decrease in tension of the tissue after maximal contraction induced by phenylephrine. Data are normalized to maximal pre-contraction ± SEM. T, testosterone; L-NAME, N(ω)-nitro-L-arginine methyl ester; PAG, DL-propargylglycine; BCA, β-cyano-alanine, Glim; Glibenclamide; SEM, standard error of mean. Statistical analysis was performed using multiple t-testing. *P < .05, **P < .01, ***P < .001, ****P < .0001.
Figure 3
Figure 3
Isometric tension measurement assay of human corpus cavernosum tissue investigating the effect of flutamide on the relaxation induced by T. The Y-axis represents the relative decrease in tension of the tissue after maximal contraction induced by phenylephrine. Data are normalized to maximal pre-contraction ± SEM. T, testosterone; Flut, flutamide; SEM, standard error of mean. Statistical analysis was performed using multiple t-testing. *P < .05, **P < .01, ***P < .001, ****P < .0001.
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References

    1. Chemes H.E. Infancy is not a quiescent period of testicular development. Int J Androl. 2001;24:2–7. - PubMed
    1. Heemers H.V., Tindall D.J. Androgen receptor (AR) coregulators: a diversity of functions converging on and regulating the AR transcriptional complex. Endocr Rev. 2007;28:778–808. - PubMed
    1. Radmayr C., Lunacek A., Schwentner C. 5-alpha-reductase and the development of the human prostate. Indian J Urol. 2008;24:309–312. - PMC - PubMed
    1. Mangelsdorf D.J., Thummel C., Beato M. The nuclear receptor superfamily: the second decade. Cell. 1995;83:835–839. - PMC - PubMed
    1. Cato A.C., Skroch P., Weinmann J. DNA sequences outside the receptor-binding sites differently modulate the responsiveness of the mouse mammary tumour virus promoter to various steroid hormones. EMBO J. 1988;7:1403–1410. - PMC - PubMed