Androgenic regulation of NO availability in rat penile erection.
Prior studies from this laboratory, using untreated castrated (CASTRATE) rats and testosterone-treated castrated (TESTO) rats, have shown that the magnitude of the intracavernosal pressure increase during erection is androgen dependent. Studies from this and other laboratories have also presented evidence suggesting that penile erection is mediated principally by nitric oxide (NO). The present report was designed to confirm that androgens maintain the availability of cavernosal NO and to determine if this androgenic action is exerted at the genomic level modulating the expression of the neuronal form of the nitric oxide synthase gene (nNOS). The results showed that administration of supplemental L-arginine failed to augment the erectile response in either group, suggesting that substrate availability is not a cause of the reduced response in CASTRATE animals. Inhibition of NO synthesis with a nitro-arginine competitive inhibitor of nitric oxide synthase enzyme protein (NOS) resulted in strong inhibition of erection in both TESTO and CASTRATE rats. When given in conjunction with ganglionic stimulation to induce erection, the NO releasing drug, sodium nitro-prusside (SNP), increased intracavernosal pressure in CASTRATE rats but not in TESTO rats, suggesting a deficiency of the available NO in CASTRATE-animals. Finally, reverse transcription-polymerase chain reaction (RT-PCR) demonstrated that mRNA levels for the enzyme nNOS in the penis were greater in TESTO animals than in CASTRATE rats. These results support the hypothesis that androgens mediate the erectile response in the rat penis by stimulating the expression of the neuronal isoform of nitric oxide synthase, thus maintaining an adequate supply of NO.
Reilly
C M
CM
Department of Physiology and Endocrinology, Medical College of Georgia, Augusta 30912-3000, USA.
Zamorano
P
P
Stopper
V S
VS
Mills
T M
TM
D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D004558:Electric Stimulation; D015971:Gene Expression Regulation, Enzymologic; D008297:Male; D009474:Neurons / Q000201:enzymology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D019335:Nitroarginine / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D009919:Orchiectomy; D010410:Penile Erection / Q000187:drug effects / Q000502:physiology*; D010413:Penis / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D013739:Testosterone / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
D012333:RNA, Messenger; D009599:Nitroprusside; D019335:Nitroarginine; D009569:Nitric Oxide; D013739:Testosterone; D001120:Arginine; D019001:Nitric Oxide Synthase