title: Update on corpus cavernosum smooth muscle contractile pathways in erectile function: a role for testosterone?
abstract: BACKGROUND
  Normal erectile function (EF) involves a coordinated relaxation of the arteries that supply the penis and the corpus cavernosum smooth muscle (CCSM), resulting in expansion of the sinusoids and increased intracavernous pressure. But the CCSM spends the majority of its time in the contracted state which is mediated by norepinephrine released from nerve endings and other vasoconstrictors like endothelins released from the endothelium. These agents cause smooth muscle myosin (SMM) phosphorylation by elevating intracellular calcium. When calcium returns to basal levels, the calcium sensitivity increases and prevents myosin dephosphorylation, which involves the RhoA/Rho-kinase (ROK) mechanism, thus maintaining force. Although mounting evidences demonstrate that androgens have a major influence on EF that is not just centrally mediated, this notion remains quite controversial.
  
  
  OBJECTIVE
  To summarize the current knowledge on CCSM contractile pathways, the role they play in modulating EF, and the influence of androgens.
  
  
  METHODS
  The article reviews the literature and contains some previously unpublished data on CCSM contraction signaling including the role that androgens are known to play in modulating these pathways.
  
  
  METHODS
  Data from peer-reviewed publications and previously unpublished observations.
  
  
  RESULTS
  In addition to downregulation of many pro-erectile molecular mechanisms, decreased testosterone (T) levels upregulate CCSM contractility, including hyperresponsiveness to α-adrenergic agonists, increased SMM phosphorylation, alteration of SMM isoform composition, activation of RhoA/ROK signaling and modulation of sphingosine-1-phosphate regulation of CCSM tone.
  
  
  CONCLUSIONS
  Decreased T levels upregulate CCSM contractile signaling. Meanwhile, it downregulates CCSM relaxation pathways synergizing to produce erectile dysfunction (ED). Although some urologists and researchers are still skeptical of the influence of androgens on penile erection, understanding these molecular control mechanisms as well as the influence that androgens have on these pathways should provide new evidence supporting the roles of androgens in EF and enhance the discovery of novel targets for drug development to treat ED.
authors.affiliation: Department of Surgery/Division of Urology, Cooper University Hospital, Camden, NJ, USA Department of Urology, First Affiliated Hospital of Guangxi Medical University, Nanning, China.
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Zhang
authors.forename: Arnold
authors.initials: A
authors.lastname: Melman
authors.forename: Michael E
authors.initials: ME
authors.lastname: Disanto
mesh_terms: D000818:Animals; D004285:Dogs; D006801:Humans; D008297:Male; D009119:Muscle Contraction / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D009919:Orchiectomy; D010410:Penile Erection / Q000502:physiology*; D010413:Penis / Q000502:physiology*; D051381:Rats; D013739:Testosterone / Q000502:physiology*
chemical_list: D013739:Testosterone