Abstract
BackgroundMany men suffering from stress, including post-traumatic stress disorder (PTSD), report sexual dysfunction, which is traditionally treated via psychological counseling. Recently, we identified a gastrin-releasing peptide (GRP) system in the lumbar spinal cord that is a primary mediator for male reproductive functions.Methodology/Principal FindingsTo ask whether an acute severe stress could alter the male specific GRP system, we used a single-prolonged stress (SPS), a putative rat model for PTSD in the present study. Exposure of SPS to male rats decreases both the local content and axonal distribution of GRP in the lower lumbar spinal cord and results in an attenuation of penile reflexes in vivo. Remarkably, pharmacological stimulation of GRP receptors restores penile reflexes in SPS-exposed males, and induces spontaneous ejaculation in a dose-dependent manner. Furthermore, although the level of plasma testosterone is normal 7 days after SPS exposure, we found a significant decrease in the expression of androgen receptor protein in this spinal center.Conclusions/SignificanceWe conclude that the spinal GRP system appears to be a stress-vulnerable center for male reproductive functions, which may provide new insight into a clinical target for the treatment of erectile dysfunction triggered by stress and psychiatric disorders.
Highlights
Post-traumatic stress disorder (PTSD) is a psychiatric disorder involving long-lasting symptoms that may occur after exposure to a life-threatening traumatic event, and is characterized by intrusive memories, a hyperarousal state and avoidance of stimuli associated with the trauma [1]
Effects of single-prolonged stress (SPS) on the gastrin-releasing peptide (GRP) content in the lumbar spinal cord Using a competitive enzyme-linked immunosorbent assay (ELISA) specific for GRP, we quantified the local contents of GRP in two separate regions of the lumbar spinal cord by dividing the lumbar spinal cord into upper (L3–4; somal region of GRP neurons; Fig. 1A–C) and lower (L5–6; axonal region of GRP neurons; Fig. 1A, B, D) spinal regions
We recently demonstrated that most GRP neurons in the lumbar spinal cord express androgen receptor (AR), but not estrogen receptor alpha (ERa) [20]
Summary
Post-traumatic stress disorder (PTSD) is a psychiatric disorder involving long-lasting symptoms that may occur after exposure to a life-threatening traumatic event, and is characterized by intrusive memories (flashbacks), a hyperarousal state and avoidance of stimuli associated with the trauma [1]. Clinical data have indicated increased rates of sexual dysfunction, including erection and ejaculation difficulties in patients with PTSD [2,3,4]. Most combat veterans with PTSD experience clinically relevant sexual difficulties and 69% have erectile dysfunction (ED) [5]. Previous studies of stress and the hypothalamic-pituitary-gonadal axis have indicated that circulating testosterone (T) fluctuates in response to physical and psychological stress [7,8,9]. As opposed to other stress-related diseases, there is evidence that plasma or serum T levels do not change in combat-related PTSD patients [10] or in refugees suffering from PTSD [11]. Many men suffering from stress, including post-traumatic stress disorder (PTSD), report sexual dysfunction, which is traditionally treated via psychological counseling. We identified a gastrin-releasing peptide (GRP) system in the lumbar spinal cord that is a primary mediator for male reproductive functions
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