Articles

Re: Mariarosaria Bucci, Vincenzo Mirone, Annarita Di Lorenzo, et al. Hydrogen Sulphide Is Involved in Testosterone Vascular Effect. Eur Urol 2009;56:378–84

By: B. Srilatha and P. Ganesan Adaikanlowast

Published online: 01 January 2010

Abstract Full Text Full Text PDF (61 KB)

Refers to article:

Hydrogen Sulphide Is Involved in Testosterone Vascular Effect

Mariarosaria Bucci, Vincenzo Mirone, Annarita Di Lorenzo, Valentina Vellecco, Fiorentina Roviezzo, Vincenzo Brancaleone, Imbimbo Ciro and Giuseppe Cirino

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 [1] 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 [2], [3], and [4], 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 [5]. Presently, together with the identified role of testosterone in this pathway (in the thoracic aorta) by Bucci and coworkers [1], 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 [3] and [4]. 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 [6], 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.

References

  • [1] M. Bucci, V. Mirone, A. Di Lorenzo, et al. Hydrogen sulphide is involved in testosterone vascular effect. Eur Urol. 2009;56:378-384 Abstract, Full-text, PDF, Crossref.
  • [2] B. Srilatha, P.G. Adaikan, P.K. Moore. Possible role for the novel gasotransmitter hydrogen sulphide in erectile dysfunction-a pilot study. Eur J Pharmacol. 2006;535:280-282 Crossref.
  • [3] B. Srilatha, P.G. Adaikan, L. Li, P.K. Moore. Hydrogen sulphide: a novel endogenous gasotransmitter facilitates erectile function. J Sex Med. 2007;4:1304-1311
  • [4] B. Srilatha, L. Hu, P.G. Adaikan, P.K. Moore. Initial characterization of hydrogen sulphide effects in female sexual function. J Sex Med. 2009;6:1875-1884 Crossref.
  • [5] 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 Crossref.
  • [6] N. Shukla, G. Rossoni, M. Hotston, et al. Effect of hydrogen sulphide-donating sildenafil (ACS6) on erectile function and oxidative stress in rabbit isolated corpus cavernosum and in hypertensive rats. BJU Int. 2009;103:1522-1529 Crossref.

Footnotes

Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University Hospital, National University of Singapore, Singapore

lowast 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.