madman
Super Moderator
THE SCIENCE AND PRACTICE OF ERECTION PHYSIOLOGY: STORY OF A REVOLUTIONARY GASEOUS MOLECULE
Abstract
The field of sexual medicine, in reference to the science of the sexual response and the clinical management of sexual dysfunctions, has evolved remarkably in the last 25 years. Erection biology has been central in driving this progress and is measured considerably by the discovery, study, and clinical translation of a simple gaseous molecule, nitric oxide, which is operative in the penis. Nitric oxide functions extraordinarily as a neurotransmitter and molecular signal transducer. It is now well understood to be the principal molecular mediator of penile erection and to be a critical element involved in dysregulatory mechanisms of erection disorders ranging from erectile dysfunction to priapism. It is most familiarly associated with the scientific development of oral medications for treating erectile dysfunction, which has modernized the clinical management of this condition.
Fig. 1.
Schematic diagram of the nitric oxide signaling pathway in the penis for mediating the erection response. The diagram shows the molecular basis for erection physiology that may transition between flaccidity (erectile tissue contraction) and erection (erectile tissue relaxation) depending upon the extent of sexual stimulation. Nitric oxide is generated constitutively from L-arginine by catalysis of neuronal nitric oxide synthase (NOS) and endothelial NOS localized to neurons and endothelial cells, respectively. After its release from generator cells in the penis, nitric oxide diffuses locally to corporal smooth muscle cells whereby it activates guanylate cyclase to convert 5′-guanosine triphosphate (GTP) to 3′, 5′-cyclic guanosine monophosphate (cGMP). This cyclic nucleotide then exerts downstream effects resulting in penile erection. Phosphodiesterase type 5 (PDE5) degrades cGMP to its inactive form, 5′-GMP, which is subsequently reformed into GTP. A PDE5 inhibitor blocks PDE5 activity, thereby potentiating effector actions of cGMP.
The modern era of the science and practice of sexual medicine may well credit the scientific discoveries of nitric oxide signaling in the penis for launching PDE5 inhibitory therapy. In the realm of basic science, erection biologic studies surrounding nitric oxide paved the way for a host of subsequent investigations exploring alternative cellular and molecular mechanisms of the sexual response. Clinical research in sexual medicine ramped up with rigorous investigations of erectile dysfunction parameters including its etiologies, severities, associated clinical disease states, and affected populations. Expanded interest in understanding and investigating all forms of sexual dysfunction for both men and women was generated, and it arguably contributed to progress in the field of study of female sexual dysfunctions. The clinical practice of sexual medicine was advanced, promoting public dialogue about sexual health problems and galvanizing the medical community beyond urologists and sexual health specialists to become aware and offer treatment for these problems. Furthermore, the modern science of erections has propelled forward the conviction that sexual health is a public health concern, with evidence that its attention and treatment achieve life quality improvement and overall health maintenance (32,37,38).
Abstract
The field of sexual medicine, in reference to the science of the sexual response and the clinical management of sexual dysfunctions, has evolved remarkably in the last 25 years. Erection biology has been central in driving this progress and is measured considerably by the discovery, study, and clinical translation of a simple gaseous molecule, nitric oxide, which is operative in the penis. Nitric oxide functions extraordinarily as a neurotransmitter and molecular signal transducer. It is now well understood to be the principal molecular mediator of penile erection and to be a critical element involved in dysregulatory mechanisms of erection disorders ranging from erectile dysfunction to priapism. It is most familiarly associated with the scientific development of oral medications for treating erectile dysfunction, which has modernized the clinical management of this condition.
Fig. 1.
Schematic diagram of the nitric oxide signaling pathway in the penis for mediating the erection response. The diagram shows the molecular basis for erection physiology that may transition between flaccidity (erectile tissue contraction) and erection (erectile tissue relaxation) depending upon the extent of sexual stimulation. Nitric oxide is generated constitutively from L-arginine by catalysis of neuronal nitric oxide synthase (NOS) and endothelial NOS localized to neurons and endothelial cells, respectively. After its release from generator cells in the penis, nitric oxide diffuses locally to corporal smooth muscle cells whereby it activates guanylate cyclase to convert 5′-guanosine triphosphate (GTP) to 3′, 5′-cyclic guanosine monophosphate (cGMP). This cyclic nucleotide then exerts downstream effects resulting in penile erection. Phosphodiesterase type 5 (PDE5) degrades cGMP to its inactive form, 5′-GMP, which is subsequently reformed into GTP. A PDE5 inhibitor blocks PDE5 activity, thereby potentiating effector actions of cGMP.
The modern era of the science and practice of sexual medicine may well credit the scientific discoveries of nitric oxide signaling in the penis for launching PDE5 inhibitory therapy. In the realm of basic science, erection biologic studies surrounding nitric oxide paved the way for a host of subsequent investigations exploring alternative cellular and molecular mechanisms of the sexual response. Clinical research in sexual medicine ramped up with rigorous investigations of erectile dysfunction parameters including its etiologies, severities, associated clinical disease states, and affected populations. Expanded interest in understanding and investigating all forms of sexual dysfunction for both men and women was generated, and it arguably contributed to progress in the field of study of female sexual dysfunctions. The clinical practice of sexual medicine was advanced, promoting public dialogue about sexual health problems and galvanizing the medical community beyond urologists and sexual health specialists to become aware and offer treatment for these problems. Furthermore, the modern science of erections has propelled forward the conviction that sexual health is a public health concern, with evidence that its attention and treatment achieve life quality improvement and overall health maintenance (32,37,38).
