Molecular pathophysiology of priapism: emerging targets

Abstract

Priapism is an erectile disorder involving uncontrolled, prolonged penile erection without sexual purpose, which can lead to erectile dysfunction. Ischemic priapism, the most common of the variants, occurs with high prevalence in patients with sickle cell disease. Despite the potentially devastating complications of this condition, management of recurrent priapism episodes historically has commonly involved reactive treatments rather than preventative strategies. Recently, increasing elucidation of the complex molecular mechanisms underlying this disorder, principally involving dysregulation of nitric oxide signaling, has allowed for greater insights and exploration into potential therapeutic targets. In this review, we discuss the multiple molecular regulatory pathways implicated in the pathophysiology of priapism. We also identify the roles and mechanisms of molecular effectors in providing the basis for potential future therapies.

Fig. (1)

Schematic representation of the molecular pathophysiologic mechanisms of priapism; normal penile erection physiology depicted in inset (bottom right). A constellation of molecular factors promote uncontrolled erection (priapism) by interfering with the normal regulatory control mechanisms involved in the return of the penis back to its flaccid state. Circular arrows represent pathway between penile erection states. Horizontal black arrows represent mediation. Horizontal black T-shapes represent inhibition. Broken arrows represent both direct and indirect downstream effects of signaling pathways. Upward black arrows represent upregulation. Downward black arrows represent downregulation. NO/cGMP = nitric oxide/ cyclic guanosine monophosphate, ROS/RNS = reactive oxygen species/reactive nitrogen species, ROCK = rho-associated protein kinase, PDE5 = phosphodiesterase type 5, HO = heme oxygenase