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

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 ¼ 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/H 2 S synthesis inhibitors, a K ATP 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 ¼ .01) compared with 6.8% ± 15.9% for vehicle (dimethylsulfoxide) at 300 mM. The relaxing effect of T was not countered by blocking NO synthesis, H 2 S synthesis, K ATP 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.

Nitric Oxide Resistance in Priapism Associated with Sickle Cell Disease: Mechanisms, Therapeutic Challenges, and Future Directions.

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Comparison of short and long-acting testosterone replacement therapy for better sperm production and testosterone levels in male late-onset hypogonadism

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Role of Glucose-Lowering Medications in Erectile Dysfunction

“…Despite the aforementioned results that described direct modulation of vasodilator genes by testosterone, emerging ex vivo data suggest that androgens regulate the physiological function of SMCs in human corpora cavernosum regardless of NO-cGMP dilator pathways. In particular, supraphysiological levels of testosterone evoked relaxation responses of SMCs in explants of human corpora cavernosum from patients with ED probably via ‘nongenomic mechanisms’ [ 51 , 52 ]. In particular, the treatment of precontracted cavernosal tissue with testosterone led to cell relaxation within a few minutes, even though both NO synthesis and androgen receptors were inhibited, suggesting the involvement of noncanonical mechanisms [ 51 , 52 ].…”