The effects of testosterone deficiency on the structural integrity of the penile dorsal nerve in the rat

Abstract

Androgens play a vital role in erectile function and are known to have a neuroprotective role in the nervous system. This study investigated, in a rat model, the effects of testosterone deprivation and replacement on the morphology of the dorsal nerve of the rat penis at the light microscopy level. Two weeks after castration, male rats were infused with vehicle alone or 44 lg of testosterone for 2 weeks. Age-matched, sham-operated control animals were used for comparisons. Penile tissue samples were removed for histological analyses. The following parameters were assessed: (1) total myelin sheath thickness; (2) density of nerve fibers; and (3) axon cross-sectional area per nerve fiber. Castration resulted in a significant increase in axon cross-sectional area compared to that of the control and testosterone-treated animals (6.9770.59 lm 2 per fiber in control animals to 14.3270.44 lm 2 per fiber in castrated animals). Qualitatively, there were signs of nerve degeneration, particularly myelin sheath degeneration, in all sample groups. We did not observe statistically significant changes in myelin sheath thickness. There was a trend of reduced nerve density. Nerve degeneration was not quantified since this study was performed at the light microscopic level. This study suggests that testosterone has a neuroprotective role in the nerve fibers of the dorsal nerve and testosterone deficiency may lead to different forms of nerve degeneration resulting in anatomic alterations, thus contributing to erectile dysfunction.

Impact of androgen deprivation therapy on sexual function

“…In a study by Armagan et al, 15 2 weeks after castration, male rats started to show ultrastructural alterations of their penile dorsal nerve compared to control rats. These alterations included signs of nerve degeneration, and especially myelin sheath degeneration.…”

Translational Perspective on the Role of Testosterone in Sexual Function and Dysfunction

“…Cavernous nerves from castrated rats demonstrated decreased nerve fiber density and thinner myelin sheaths compared with intact rats or castrated rats supplemented with testosterone [22]. Evidence of neuronal degeneration, such as decreased myelin thickness, lower nerve density and smaller nerve cross-sectional area, is also seen in the dorsal nerve of the penis of castrated rats [110]. Testosterone impacts nitrergic nerves as castration revealed decreased abundance of nitric oxide synthase (NOS) in penile tissue [111, 70] and decreased NOS containing nerve fibers in the corpora cavernosa of castrated rat penis [99].…”

Testosterone, Endothelial Health, and Erectile Function

“…In addition, testosterone is also thought to regulate the structure and function of penile nerve fiber network, modulating the response to sexual stimulation. In fact, experimental studies showed that testosterone deprivation by castration altered cavernosal nerve structure and reduced the intracavernosal pressure [85–87]. These effects were reversed by testosterone supplementation [86, 87].…”