Male Sexual DysfunctionEffects of Androgen on the Expression of Vascular Endothelial Growth Factor in the Penile Corpus Cavernosum
Section snippets
Animal Subjects and Treatment Protocol
Sixty adult male Sprague-Dawley rats (12 weeks old) were used in the current study. The rats were separated into 2 groups by time after surgery (group I [n = 30], 1 week; and group II [n = 30], 2 weeks). Each group was then into a control (n = 10), surgical castration (n = 10), and castration with androgen replacement subgroup (n = 10). The control subgroup was sham-operated. Rats were castrated under ketamine anesthesia (35 mg/kg intraperitoneal [ip]) and androgen replacement was achieved by
Serum Testosterone and DHT
Serum testosterone and dihydrotestosterone (DHT) levels were significantly decreased after 1 week of castration (2.20 ± 0.85, 0.10 ± 0.15 ng/mL), which was restored to the control level (3.48 ± 0.76, 0.48 ± 0.11 ng/mL) after testosterone replacement, respectively (P <.05). The mean body weights were not significantly different between any of the treatment groups (Table 1).
Erectile Function Studies
Pelvic nerve stimulation in the castrated group elicited significantly decreased erectile responses compared with those in
Comment
There have been limited studies investigating the effects of various growth factors on nerve regeneration and cavernosal tissue remodeling and function. Given that androgens have been shown to be critical in maintaining erectile tissue structure and function in animals, we examined the relationship between androgens and growth factor expression. Because the corpus cavernosum is a vascular tissue, VEGF served as a suitable candidate that might mediate some of the effects of androgens.
VEGF acts
Conclusions
Our data further reinforce the concept that androgens are important for the maintenance of erectile function and suggest that the VEGF production is androgen-dependent. Androgen deficiency may cause downregulation of VEGF, resulting in an imbalance in connective tissue synthesis and deposition, which leads to cavernosal tissue fibrosis and erectile dysfunction. Further animal model studies are needed for the development of growth factor therapy as a novel treatment for erectile dysfunction.
Acknowledgment
This study was supported by a grant of the Korea Healthcare technology R&D Project, Ministry for Health, Welfare and family Affairs, Republic of Korea (A084869).
References (30)
- et al.
Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study
J Urol
(1994) - et al.
Sildenafil preserves intracorporeal smooth muscle after radical retropubic prostatectomy
J Urol
(2004) - et al.
The physiological role of androgens in penile erection: regulation of corpus cavernosum structure and function
J Sex Med
(2005) - et al.
PGE1 suppresses the induction of collagen synthesis by transforming growth factor-beta 1 in human corpus cavernosum smooth muscle
J Urol
(1995) - et al.
The effect of vascular endothelial growth factor on a rat model of traumatic arteriogenic erectile dysfunction
J Urol
(2002) - et al.
Vascular endothelial growth factor promotes proliferation and migration of cavernous smooth muscle cells
J Urol
(2001) - et al.
Intracavernosal injection of vascular endothelial growth factor improves erectile function in aged rats
Eur Urol
(2004) - et al.
Mechanisms of venous leakage: a prospective clinicopathological correlation of corporeal function and structure
J Urol
(1996) - et al.
Vascular endothelial growth factors are differentially regulated by steroid hormones and antiestrogens in breast cancer cells
Mol Cell Endocrinol
(1999) - et al.
Testosterone induces vascular endothelial growth factor synthesis in the ventral prostate in castrated rats
J Urol
(1999)
Vascular endothelial growth factor is up-regulated in vitro and in vivo by androgens
Biochem Biophys Res Commun
Pathomechanisms of cartilage destruction by mechanical injury
Ann Anat
The influence of biomechanical parameters on the expression of VEGF and endostatin in the bone and joint system
Ann Anat
Erectile dysfunction
N Engl J Med
Are androgens critical for penile erections in humans?Examining the clinical and preclinical evidence
J Sex Med
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2016, Journal of Sexual MedicineCitation Excerpt :Vcsa1 expression and its gene product, sialorphin, increased with testosterone supplementation after castration.28 Vascular endothelial growth factor protein and mRNA decrease in the corpora cavernosa of castrated rats and androgen replacement returned vascular endothelial growth factor to baseline expression.88 RhoA and Rho-kinase protein increased with castration, resulting in a depressed erectile response.55
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