Physiology of Erectile Function: An Update on Intracellular Molecular Processes

ObjectivesTo provide a comprehensive update of current knowledge concerning the molecular mechanisms underlying the erectile physiology.MethodsResults from numerous investigations, including both basic and clinical studies, have been considered. In particular, we pointed out the advances concerning the peripheral control of erection that ultimately influence the functional state of the penis.ResultsNumerous neurotransmitters and endothelial factors modulate the penile vasculature and smooth muscle tone of corpora cavernosa in the penis. The regulation of adequate intracellular calcium levels represents the key determinant of the smooth muscle tone. Following the sexual stimulation, the activation of smooth muscle relaxation in the penis is mainly mediated by nitric oxide (NO), which acts via cyclic guanosine monophosphate (cGMP)-mediated intracellular signalling. The pro-erectile NO/cGMP pathway is coupled to the anti-erectile RhoA/Rho-kinase calcium-sensitizing pathway, which was recently highlighted as another important regulator of the erectile function. In the last decade, the enzyme phosphodiesterase 5 (PDE5), critically involved in the degradation of cGMP and thereby in the maintenance of penile detumescence, has gained attention as target enzyme of the most used drugs (PDE5 inhibitors) for the treatment of erectile dysfunction. Moreover, androgens play an important role in peripheral regulation of erection, acting positively either on the enzyme which synthesizes NO (NOS), and on that involved in the degradation of cGMP (PDE5).ConclusionThe recent advances added to new insights into our knowledge of erectile physiology and leaded to the improvement in the clinical management of men affected by erectile dysfunction.