Vascular endothelial growth factor restores erectile function through modulation of the insulin-like growth factor system and sex hormone receptors in diabetic rat.
Previous studies have shown that intracavernous injection of vascular endothelial growth factor (VEGF) restored erectile function in diabetic rats. However, the mechanism of VEGF in diabetes-related erectile dysfunction (ED) has not been fully investigated. We hypothesize that intracavernous injection of VEGF may reverse diabetes-related ED through modulation of the insulin-like growth factor system and sex hormone receptors. To test this hypothesis the erectile function of treated and control rats was analyzed by measurement of intracavernous pressure (ICP) following electrostimulation of the cavernous nerves. Mean ICP was significantly lower in non-treated diabetic rats compared to controls. After VEGF injection, ICP was significantly higher than in non-treated diabetic rats. IGFBP-3 mRNA and protein expression was significantly higher in non-treated diabetic rat crura than controls, while VEGF-treated animals had control levels. ER-beta and PR mRNA and protein expression was significantly lower in non-treated diabetic rat crura. After VEGF injection, ER-beta and PR mRNA and protein expression was similar to control levels. Expression of AR and ER-alpha was the same in all groups. These findings suggest that orthotopic injection of VEGF may improve the functional recovery of diabetes-related ED through modulation of the insulin-like growth factor system and sex hormone receptors. To our knowledge, this is the first study demonstrating that VEGF treatment restores erectile function through restoration of the insulin-like growth factor system and sex hormone receptor genes at the mRNA and protein levels in diabetic rat crura. These results may be important in understanding the pathogenesis of diabetes-related ED and also in providing better strategies for management of this disease.
Shirai
Masato
M
Department of Urology, Veterans Affairs Medical Center and University of California at San Francisco, USA.
Yamanaka
Masaki
M
Shiina
Hiroaki
H
Igawa
Mikio
M
Kawakami
Toshifumi
T
Ishii
Nobuhisa
N
Lue
Tom F
TF
Fujime
Makoto
M
Dahiya
Rajvir
R
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D007172:Erectile Dysfunction / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D009474:Neurons / Q000187:drug effects; D010410:Penile Erection / Q000187:drug effects* / Q000502:physiology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D013002:Somatomedins / Q000235:genetics / Q000378:metabolism*; D013311:Streptozocin / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
D001786:Blood Glucose; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D013002:Somatomedins; D042461:Vascular Endothelial Growth Factor A; D013311:Streptozocin