Effects of diabetes on nitric oxide synthase and growth factor genes and protein expression in an animal model.
Erectile dysfunction occurs frequently in humans with diabetes mellitus; the molecular basis of this phenomenon is not known. We investigated the effects of diabetes on penile erection, nitric oxide synthase and growth factors expression in an animal model. Forty male rats were divided into two groups: the experimental group (n = 30) received intraperitoneal injection of Streptozotocin (STZ) dissolved in citrate buffer to induce diabetes; ten age-matched control rats received injection of citrate buffer vehicle only. Before euthanization at eight weeks, erectile function was assessed by electrostimulation of the cavernous nerves. NADPH diaphorase staining was used to identify NOS and immunostaining technique was used to identify nNOS in the penile nerve fibers. RT-PCR was used to identify mRNA expression of nNOS, eNOS, iNOS, ER-beta, ER-alpha, NGF, IGF-I, TGF-beta 1, and AR. Western blot was used to identify nNOS, IGF-I, NGF, and TFG-beta protein expressions. In the diabetic group, there was: (1) a significant decrease in NOS containing nerve fibers in the dorsal and intracavernosal nerves; (2) a significant lower maximal intracavernosal pressure. RT-PCR showed down-regulation of nNOS (large form), iNOS and ER-beta mRNA expression, Immunoblot showed down-regulation of nNOS protein expression and nNOS immunostaining showed less positive staining in the dorsal and intracavernous nerves in the diabetic group. These molecular changes may provide the basis for further studies to explore the association between diabetes and impotence.
Department of Urology, University of California, School of Medicine, San Francisco 94143-0738, USA.
A I
AI
El-Sakka
C S
CS
Lin
R M
RM
Chui
R
R
Dahiya
T F
TF
Lue
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004558:Electric Stimulation; D006133:Growth Substances / Q000032:analysis / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000235:genetics; D008297:Male; D009252:NADPH Dehydrogenase / Q000032:analysis; D009414:Nerve Growth Factors / Q000032:analysis / Q000235:genetics; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000235:genetics*; D010410:Penile Erection; D010413:Penis / Q000737:chemistry / Q000294:innervation; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011916:Rats, Inbred F344; D011960:Receptors, Estrogen / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000235:genetics
D006133:Growth Substances; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D016212:Transforming Growth Factor beta; D007334:Insulin-Like Growth Factor I; D019001:Nitric Oxide Synthase; D009252:NADPH Dehydrogenase