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Scientific Reports May 2023The human penis transmits behaviorally important sensory information via the dorsal penile nerve, which is required for initiation and maintenance of erection. The human...
The human penis transmits behaviorally important sensory information via the dorsal penile nerve, which is required for initiation and maintenance of erection. The human penis differs from the penes of other hominids. The lack of a baculum makes the human penis dependent on erectile tissue, which is under control of neural signals activated by tactile stimulation. Accordingly, the penile sensory innervation is crucial for human sexual behavior. To clarify penile innervation, we analyzed the architecture of the dorsal penile nerve of five male subjects who donated their body. We stained the sensory fibers in the penile dorsal nerve with anti-neurofilament H antibody, and identified myelinated axons with Luxol fast blue staining. Furthermore, we visualized nerve bundles as they travel along the shaft of the penis by performing microfocus computed tomography scans after counterstaining penes with iodine. Our results show that the dorsal penile nerve is organized in 25-45 loosely packed nerve bundles, running mediodorsally in the shaft of the penis. This organization corresponds to that in penes of other mammalian species, but differs from the organization of the other peripheral sensory nerves. Around half of the dorsal penile nerve fibers were myelinated and a human hemipenis contained a total of 8290 ± 2553 (mean ± SD) axons. Thus, the number of sensory axons in the human dorsal penile nerve is higher than in other species described so far. The large fraction of unmyelinated nerve fibers suggests that the conduction speed is not a crucial aspect of penile sensory transmission.
Topics: Animals; Humans; Male; Pudendal Nerve; Penis; Penile Erection; Axons; Peripheral Nerves; Mammals
PubMed: 37258532
DOI: 10.1038/s41598-023-35030-w -
Andrologia Dec 2015Cigarette smoking is a leading cause of preventable morbidity and mortality in the United States. Although public policies have resulted in a decreased number of new... (Review)
Review
Cigarette smoking is a leading cause of preventable morbidity and mortality in the United States. Although public policies have resulted in a decreased number of new smokers, smoking rates remain stubbornly high in certain demographics with 20% of all American middle-aged men smoking. In addition to the well-established harmful effects of smoking (i.e. coronary artery disease and lung cancer), the past three decades have led to a compendium of evidence being compiled into the development of a relationship between cigarette smoking and erectile dysfunction. The main physiologic mechanism that appears to be affected includes the nitric oxide signal transduction pathway. This review details the recent literature linking cigarette smoking to erectile dysfunction, epidemiological associations, dose dependency and the effects of smoking cessation on improving erectile quality.
Topics: Erectile Dysfunction; Humans; Male; Penile Erection; Smoking; Smoking Cessation
PubMed: 25557907
DOI: 10.1111/and.12393 -
The Journal of Sexual Medicine Mar 2009Immunophilin ligands provide potentially new alternatives for the treatment of erectile dysfunction (ED), which occurs after injury of the cavernous nerves (CNs). (Review)
Review
INTRODUCTION
Immunophilin ligands provide potentially new alternatives for the treatment of erectile dysfunction (ED), which occurs after injury of the cavernous nerves (CNs).
AIM
To review and update current knowledge of the neurotrophic effects and likely mechanism of action of immunophilin proteins with emphasis on the FK506-binding protein (FKBP) subfamily and the role of immunophilin ligands for the treatment of CN injury-induced ED.
METHODS
Review of available reports of studies investigating the effects and neurotrophic mechanisms of immunophilin ligands involved in erectile function recovery in rodent models of CN injury.
MAIN OUTCOME MEASURES
Erection parameters and molecular correlations associated with CN injury and functional recovery.
RESULTS
Treatment with prototype immunosuppressive immunophilin ligands FK506 (FK) and rapamycin (Rapa) improve erectile function in animal models of CN injury. Similarly, non-immunosuppressive analogs such as GPI-1046 and FK1706 are effective in recovery of erections after CN injury. Neuronal nitric oxide may influence the erection recovery effects of immunophilin ligands after CN injury. FKBPs 38 and 65 expression changes in the penis and its innervation coincide with the neurotrophic effects of immunophilin ligands. Antioxidative actions of immunophilin ligands contribute to their neurotrophic effects. Immunophilins are localized to nerves coursing in human prostate and penile tissue.
CONCLUSIONS
The findings support the hypothesis that immunophilin ligands, working through specific receptor mechanisms that are specific to injured CN, are potentially useful to sustain erectile function in men following radical prostatectomy.
Topics: Animals; Erectile Dysfunction; Immunophilins; Ligands; Male; Mice; Nerve Regeneration; Nitric Oxide; Penile Erection; Penis; Peripheral Nerve Injuries; Recovery of Function; Tacrolimus Binding Proteins
PubMed: 19267858
DOI: 10.1111/j.1743-6109.2008.01193.x -
Clinical Science (London, England :... Jul 2017The principle steroidal androgens are testosterone and its metabolite 5α-dihydrotestosterone (DHT), which is converted from testosterone by the enzyme 5α-reductase.... (Review)
Review
The principle steroidal androgens are testosterone and its metabolite 5α-dihydrotestosterone (DHT), which is converted from testosterone by the enzyme 5α-reductase. Through the classic pathway with androgens crossing the plasma membrane and binding to the androgen receptor (AR) or via mechanisms independent of the ligand-dependent transactivation function of nuclear receptors, testosterone induces genomic and non-genomic effects respectively. AR is widely distributed in several tissues, including vascular endothelial and smooth muscle cells. Androgens are essential for many developmental and physiological processes, especially in male reproductive tissues. It is now clear that androgens have multiple actions besides sex differentiation and sexual maturation and that many physiological systems are influenced by androgens, including regulation of cardiovascular function [nitric oxide (NO) release, Ca mobilization, vascular apoptosis, hypertrophy, calcification, senescence and reactive oxygen species (ROS) generation]. This review focuses on evidence indicating that interplay between genomic and non-genomic actions of testosterone may influence cardiovascular function.
Topics: Androgens; Apoptosis; Cardiovascular Diseases; Cardiovascular Physiological Phenomena; Cardiovascular System; DNA; Genomics; Humans; Kidney; Penile Erection; Reactive Oxygen Species; Receptors, Androgen; Testosterone
PubMed: 28645930
DOI: 10.1042/CS20170090 -
Journal of Andrology 2012Hydrogen sulfide (H(2)S), which is a well-known toxic gas, has recently been recognized as a biological messenger that plays an important role in physiological and... (Review)
Review
Hydrogen sulfide (H(2)S), which is a well-known toxic gas, has recently been recognized as a biological messenger that plays an important role in physiological and pathophysiological conditions. Relatively high levels of H(2)S have been discovered in mammalian tissues. It is mainly synthesized by 2 enzymes, including cystathionine β-synthase and cystathionine γ-lysase, which utilize L-cysteine as substrate to produce H(2)S. H(2)S has been demonstrated to exhibit potent vasodilator activity both in vitro and in vivo by relaxing vascular smooth muscle. Recently, H(2)S has been discovered in penile tissue with smooth muscle relaxant effects. Furthermore, other effects of H(2)S could play a role in the physiology of erection. Understanding H(2)S in the physiology of erection might provide alternative erectile dysfunction strategies for those patients with poor or no response to type 5 phosphodiesterase inhibitors. This review intends to present the H(2)S pathway in penile tissue and the potential role of H(2)S in the physiology of erections.
Topics: Erectile Dysfunction; Humans; Hydrogen Sulfide; Male; Penile Erection; Penis; Phosphodiesterase 5 Inhibitors
PubMed: 22016355
DOI: 10.2164/jandrol.111.014936 -
International Journal of Molecular... Jan 2023Current literature has indicated that Peyronie's disease (PD) could be initiated by microtrauma and the subsequent inflammation episodes that follow. PD could be sorted... (Review)
Review
Current literature has indicated that Peyronie's disease (PD) could be initiated by microtrauma and the subsequent inflammation episodes that follow. PD could be sorted into acute or chronic status, and it can differ when selecting the clinical therapeutics. PD would cause pain and penile deformity to diseased men and impair their erectile function. Occasionally, surgical revision of the penis might be needed to correct the penile curvature. We find that there are limited effective options of intra-lesion injections for the PD plaques. By searching the databases and screening the literature with the PRISMA 2020 guideline, we observed that several preclinical studies that applied stem cell therapy in treating PD were fruitful in the acute phase. Although in the chronic phase of PD, erectile parameters were not significantly improved, and therefore, future studies might be better elevated in certain aspects, such as the sites selected for harvesting stem cells or changing the centrifugation forces. In this review, we concluded the contemporary understanding of inflammatory microenvironments in PD, the stem cell therapy in PD, and our perspectives on future studies. We concluded that there may be great potential in stem cell therapy for treating both acute and chronic phases PD.
Topics: Male; Humans; Penile Induration; Penis; Penile Erection; Injections; Stem Cells
PubMed: 36614220
DOI: 10.3390/ijms24010777 -
Journal of Andrology 2004
Review
Topics: Animals; Autonomic Nervous System; Clinical Trials as Topic; Erectile Dysfunction; Humans; Male; Neural Pathways; Penile Erection; Penis; Peptides, Cyclic; Receptors, Melanocortin; alpha-MSH
PubMed: 15292097
DOI: 10.1002/j.1939-4640.2004.tb02842.x -
The Journal of Sexual Medicine Jun 2008Thirty million men in the United States suffer from erectile dysfunction (ED) and this number is expected to double by 2025. Considered a major public health problem,... (Review)
Review
INTRODUCTION
Thirty million men in the United States suffer from erectile dysfunction (ED) and this number is expected to double by 2025. Considered a major public health problem, which seriously affects the quality of life of patients and their partners, ED becomes increasingly prevalent with age and chronic smoking is a major risk factor in the development of ED.
AIM
To review available evidence concerning the effects of cigarette smoking on vascular changes associated with decreased nitric oxide (NO) bioavailability and increased reactive oxygen species (ROS) generation.
METHODS
We examined epidemiological and clinical data linking cigarette smoking and ED, and the effects of smoking on vascular NO bioavailability and ROS generation.
MAIN OUTCOME MEASURES
There are strong parallels between smoking and ED and considerable evidence supporting the concept that smoking-related ED is associated with reduced bioavailability of NO because of increased ROS.
RESULTS
Cigarette smoking-induced ED in human and animal models is associated with impaired arterial flow to the penis or acute vasospasm of the penile arteries. Long-term smoking produces detrimental effects on the vascular endothelium and peripheral nerves and also causes ultrastructural damage to the corporal tissue, all considered to play a role in chronic smoking-induced ED. Clinical and basic science studies provide strong indirect evidence that smoking may affect penile erection by the impairment of endothelium-dependent smooth muscle relaxation or more specifically by affecting NO production via increased ROS generation. Whether nicotine or other products of cigarette smoke mediate all effects related to vascular damage is still unknown.
CONCLUSIONS
Smoking prevention represents an important approach for reducing the risk of ED. The characterization of the components of cigarette smoke leading to ED and the mechanisms by which these components alter signaling pathways activated in erectile responses are necessary for a complete comprehension of cigarette smoking-associated ED.
Topics: Animals; Endothelium, Vascular; Erectile Dysfunction; Humans; Male; Nitric Oxide; Oxidative Stress; Penile Erection; Reactive Oxygen Species; Smoking
PubMed: 18331273
DOI: 10.1111/j.1743-6109.2008.00804.x -
Asian Journal of Andrology Mar 2006To summarize recent advances in human penile anatomy, hemodynamics and their clinical applications.
AIM
To summarize recent advances in human penile anatomy, hemodynamics and their clinical applications.
METHODS
Using dissecting, light, scanning and transmission electron microscopy the fibroskeleton structure, penile venous vasculature, the relationship of the architecture between the skeletal and smooth muscles, and erection hemodynamics were studied on human cadaveric penises and clinical patients over a period of 10 years.
RESULTS
The tunica albuginea of the corpora cavernosa is a bi-layered structure with inner circular and outer longitudinal collagen bundles. Although there is no bone in the human glans, a strong equivalent distal ligament acts as a trunk of the glans penis. A guaranteed method of local anesthesia for penile surgeries and a tunical surgery was developed accordingly. On the venous vasculature it is elucidated that a deep dorsal vein, a couple of cavernosal veins and two pairs of para-arterial veins are located between the Buck's fascia and the tunica albuginea. Furthermore, a hemodynamic study suggests that a fully rigid erection may depend upon the drainage veins as well, rather than just the intracavernosal smooth muscle. It is believed that penile venous surgery deserves another look, and that it may be meaningful if thoroughly and carefully performed. Accordingly, a penile venous surgery was developed.
CONCLUSION
Using this new insight into penile anatomy and physiology, exact penile curvature correction, refined penile implants and promising penile venous surgery, as well as a venous patch, for treating Peyronie's deformity might be performed under pure local anesthesia on an outpatient basis.
Topics: Erectile Dysfunction; Hemodynamics; Humans; Male; Muscle, Skeletal; Muscle, Smooth, Vascular; Penile Erection; Penis
PubMed: 16491276
DOI: 10.1111/j.1745-7262.2006.00108.x -
Endocrinology and Metabolism Clinics of... Jun 1996Although the overall incidence of erectile dysfunction in the general population between the ages of 40 and 70 years is 52%, men with diabetes mellitus have impotence at... (Review)
Review
Although the overall incidence of erectile dysfunction in the general population between the ages of 40 and 70 years is 52%, men with diabetes mellitus have impotence at an earlier age and with a significantly higher prevalence, ranging as high as 75%. Numerous advances have been made in understanding the physiologic and biochemical mechanisms controlling penile erection. Improved clinical techniques for the diagnosis and treatment of impotence, including dynamic vascular testing, intracavernosal pharmacotherapy, and microsurgical revascularization, have allowed us to enter a new and exciting era in the quest for a more complete understanding of erectile dysfunction.
Topics: Adult; Aged; Diabetes Complications; Diabetes Mellitus; Erectile Dysfunction; Humans; Incidence; Male; Middle Aged; Muscle, Smooth; Penile Erection; Penis; Sexual Dysfunctions, Psychological
PubMed: 8799705
DOI: 10.1016/s0889-8529(05)70329-7