Refers to article:
Hydrogen Sulphide Is Involved in Testosterone Vascular Effect
Accepted 7 May 2008
August 2009 (Vol. 56, Issue 2, pages 378 - 384)
Understanding the dynamics of the testosterone effect in men is important because of its role in sexual and reproductive functions. Although androgen decline manifests as impaired libido and erectile dysfunction (ED), the absence of complete recovery of ED with testosterone treatment indicates that other factors are also involved in the causation and/or maintenance of this hormonal sexual dysfunction. The article by Bucci et al  highlights the importance of another possible mechanism to address in the clinical management of this unresolved quality-of-life concern.
Recently, the novel gasotransmitter hydrogen sulfide (H2S) has emerged as an important signaling pathway in several systemic functions together with its identified endogenous formation from thiol-containing amino acids. However, its functional role in sexual medicine has not been fully elucidated. In our pioneering explorations in male and female genital tissues from animal models , , and , H2S acted partly through nitric oxide (NO)–cyclic 3′,5′-guanosine monophosphate (cGMP), cyclic adenosine monophosphate (cAMP), and K+ adenosine triphosphate (K+ ATP) channels to facilitate penile and clitoral cavernosal and vaginal smooth muscle relaxations. Together with the existence of the H2S-forming enzymes cystathionine γ-lyase and cystathionine β-synthase messenger RNA and protein and their biosynthesis in these genital tissues, the interactions with the essential signaling molecules of sexual functioning formed the basis of our hypothesis that H2S complemented NO in its effects. Our experimental findings were subsequently supported by the evidence for H2S effects in the human male erectile tissue . Presently, together with the identified role of testosterone in this pathway (in the thoracic aorta) by Bucci and coworkers , we are a bit closer to the holistic understanding of the H2S concept in the area of sexual medicine.
Even though there has been worldwide use of phosphodiesterase type 5 inhibitors (PDE5Is) for the treatment of ED, there are nonresponders; therefore, the search or need for an alternative mechanism continues. In our pilot studies, the H2S-induced erection showed better qualitative characteristics compared with that produced by the PDE5I  and . Together with its advantage on the cAMP system, H2S may possess the unique quality of working through both of the important second messengers (cGMP and cAMP) of erectile functioning. In this line of research, an H2S-releasing sildenafil compound inhibited superoxide formation and significantly improved cavernosal relaxation in the rat model , confirming the promise of such an additive therapeutic combination of cAMP elevation and PDE5 inhibition. Now it seems that testosterone, through its effects on the H2S–K+ ATP pathway, may further contribute to the common mediation of successful erectile function.
New targets for potential therapy depend on such evidence-based clinical translations. This understanding is definitely needed for the future therapeutic exploitation of the H2S moiety in the area of sexual medicine.
Conflicts of interest
The authors have nothing to disclose.
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-  R. d’Emmanuele di Villa Bianca, R. Sorrentino, P. Maffia, et al. Hydrogen sulfide as a mediator of human corpus cavernosum smooth-muscle relaxation. Proc Natl Acad Sci USA. 2009;106:4513-4518
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Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Hospital, National University of Singapore, Singapore
Corresponding author. Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Hospital, National University of Singapore, 5 Lower Kent Ridge Road, Singapore 119072. Tel. +65 6772 4128/4261; Fax: +65 6779 4753.
© 2009 European Association of Urology, Published by Elsevier B.V.