The Neurobiology of Psychogenic Erectile Dysfunction in the Spinal Cord

Abstract

We recently reported a previously unknown peptidergic system within the lumbosacral spinal cord that uses gastrin-releasing peptide (GRP) to trigger erection and ejaculation in male rats. Many men suffering from stress, including posttraumatic stress disorder (PTSD) and major depressive disorder, report sexual dysfunction. Sexual dysfunction in men suffering from stress and major depressive disorder is traditionally treated via psychological counseling. To determine whether acute severe stress could alter the male-specific GRP system, we used single prolonged stress (SPS) exposure in a putative rat model for PTSD. Exposure of male rats to SPS decreases the local content and the axonal distribution of GRP in the lower lumbar spinal cord and results in an attenuation of penile reflexes in vivo. Pharmacological stimulation of GRP receptors remarkably restores penile reflexes in SPS-exposed male rats and in castrated male rats. The administration of a GRP agonist to these animal models interestingly induces spontaneous ejaculation in a dose-dependent manner. Furthermore, although the circulating level of androgens is normal 1 week after SPS exposure, there is a significant decrease in the expression of androgen receptor protein in lumbar segments 3 and 4 of the spinal cord. This might make the spinal center less responsive to androgens. In this report, I review findings on a recently identified spinal GRP system that could be vulnerable to stress and that controls male reproductive function. This system provides new insights into the clinical treatment of psychogenic erectile dysfunction triggered by stress and psychiatric disorders.