Update on corpus cavernosum smooth muscle contractile pathways in erectile function

A role for testosterone?

Xin Hua Zhang, Arnold Melman, Michael E. Disanto

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Introduction. 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. Aim. 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 The article reviews the literature and contains some previously unpublished data on CCSM contraction signaling including the role that androgens are known to play in modulating these pathways. Main Outcome Measures. Data from peer-reviewed publications and previously unpublished observations.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.

Original languageEnglish (US)
Pages (from-to)1865-1879
Number of pages15
JournalJournal of Sexual Medicine
Volume8
Issue number7
DOIs
StatePublished - Jul 2011
Externally publishedYes

Fingerprint

Smooth Muscle
Testosterone
Androgens
Smooth Muscle Myosins
rho-Associated Kinases
Erectile Dysfunction
Calcium
Up-Regulation
Down-Regulation
Phosphorylation
Penile Erection
Adrenergic Agonists
Muscle Relaxation
Nerve Endings
Endothelins
Penis
Vasoconstrictor Agents
Myosins
Muscle Contraction
Endothelium

Keywords

  • Erectile function
  • Hypogonadism
  • Peripheral effects of testosterone on penile smooth muscle
  • Smooth muscle contraction
  • Testosterone

ASJC Scopus subject areas

  • Urology
  • Obstetrics and Gynecology
  • Reproductive Medicine

Cite this

Update on corpus cavernosum smooth muscle contractile pathways in erectile function : A role for testosterone? / Zhang, Xin Hua; Melman, Arnold; Disanto, Michael E.

In: Journal of Sexual Medicine, Vol. 8, No. 7, 07.2011, p. 1865-1879.

Research output: Contribution to journalArticle

Zhang, Xin Hua ; Melman, Arnold ; Disanto, Michael E. / Update on corpus cavernosum smooth muscle contractile pathways in erectile function : A role for testosterone?. In: Journal of Sexual Medicine. 2011 ; Vol. 8, No. 7. pp. 1865-1879.
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