Role of hydrogen sulfide in the physiology of penile erection

Abstract

Hydrogen sulfide (H(2)S), which is a well-known toxic gas, has recently been recognized as a biological messenger that plays an important role in physiological and pathophysiological conditions. Relatively high levels of H(2)S have been discovered in mammalian tissues. It is mainly synthesized by 2 enzymes, including cystathionine β-synthase and cystathionine γ-lysase, which utilize L-cysteine as substrate to produce H(2)S. H(2)S has been demonstrated to exhibit potent vasodilator activity both in vitro and in vivo by relaxing vascular smooth muscle. Recently, H(2)S has been discovered in penile tissue with smooth muscle relaxant effects. Furthermore, other effects of H(2)S could play a role in the physiology of erection. Understanding H(2)S in the physiology of erection might provide alternative erectile dysfunction strategies for those patients with poor or no response to type 5 phosphodiesterase inhibitors. This review intends to present the H(2)S pathway in penile tissue and the potential role of H(2)S in the physiology of erections.

Fig.1. Distribution of H₂S-producing associated enzymes in penile tissue

H₂S-producing associated enzymes were demonstrated to localize in smooth muscle cells (CBS, CSE) and nerve terminal (CSE) within the corpus caversnosum. H₂S-synthesizing associated enzymes including CBS, 3MTS and CAT were found in vascular endothelial cells. Even without direct evidence, endothelial cells in corpus cavernosum might contain these enzymes. Abbreviations: CBS= cystathionine β-synthase, CSE= cystathionine γ-lyase, 3MTS=3-mercaptopyruvate sulfurtransferase, CAT= cysteine aminotransferase.

Fig. 2. Smooth muscle relaxant effect of H₂S in corpus cavernosum

Three possible mechanisms are involved in H₂S relaxing smooth muscle cells in corpus cavernosum: 1. Activating of K_ATP channel and K_Ca channel and inducing membrane hyperpolarization. 2. Inhibiting the activity of PDE5 and breakdown of cGMP. 3. Enhancing endothelial cells to release EDRFs or/and EDHFs. 4. Activation of TRPA1 ion channels. Abbreviations: PDE5= type 5 phosphodiesterase, cGMP=3’,5’-cyclic guanosine monophosphate, EDRFs= endothelium-derived relaxant factors, EDHFs= endothelium-derived hyperpolarization factors, TRPA1= transient receptor potential A1.