Erectile dysfunction (ED) is a major complication of diabetes mellitus (DM). This study investigates the relationship between ED and the downregulation of constitutive nitric oxide synthase (cNOS) in the corpus cavernosum (CC) of diabetic rats. It also examines the effects of udenafil, a phosphodiesterase type 5 (PDE5) inhibitor, on ED and cNOS expression levels. After 16 weeks of daily oral treatment with udenafil in diabetic rats, the intracavernous pressure/mean arterial pressure (ICP/MAP) ratio was recorded to measure erectile function, and cNOS expression was measured using reverse transcriptase (RT)-PCR and immunoblots. Although the ICP/ MAP ratio and the expression levels of endothelial NOS (eNOS) and neuronal NOS (nNOS) in the CC were markedly decreased in diabetic rats, long-term udenafil treatment improved the erectile function and increased cNOS expression compared with diabetic controls. These findings suggest that ED in DM is closely related to decreased cNOS expression in the CC and that udenafil has the ability to compensate for this pathological change by modulating cNOS expression. Udenafil also has an inhibitory role in cyclic guanosine monophosphate (cGMP) degradation.

This study was performed to evaluate the effects of thyroid-stimulating hormone (TSH) on phosphatidylinositol-4-phosphate 5-kinase type IIgamma (PIPKIIgamma) gene expression in the thyrocytes of FRTL-5 cells. Although PIPKIIgamma mRNA was expressed constantly in the absence of added TSH, its expression increased remarkably in the presence of 10(-9) M TSH. This increase started within 6 h of the addition of TSH, and reached a maximum at 8 h. The mRNA expression properties of PIPKIIgamma in the cells were identified using inhibitors. Actinomycin D blocked PIPKIIgamma transcription strongly, while cycloheximide did not. In an experiment using 5,6-dichlo-1-beta-d -ribofuranosylbenzimidaxole, the half-life of PIPKIIgamma mRNA was approximately 6 h in the presence or absence of TSH, and it was not affected by the stability of the PIPKIIgamma mRNA. The effects of TSH on PIPKIIgamma gene expression were specific, and other growth factors examined (transferrin, insulin and hydrocortisone) did not alter its expression. It is possible that the mechanism of PIPKIIgamma gene expression is involved in the permissive effect of the TSH-cAMP cascade proper. Our results indicate, for the first time, that the expression of PIPKIIgamma is regulated transcriptionally by TSH in thyrocytes.

To investigate the pathogenesis of hyperlipidemia-related erectile dysfunction and the effects of DA-8159, a new phosphodiesterase-5 inhibitor, on protein expression, we performed a proteomic analysis of differentially expressed proteins in the corpus cavernosum of hyperlipidemic rats by two-dimensional electrophoresis-mass spectrometry. Rats were fed high-cholesterol diet and treated with 5 mg·kg(-1)·day(-1) DA-8159 concurrently. After 5 months apparent hyperlipidemia and significantly decreased maximal intra-cavernous pressure were observed in the control group with the alteration of 8 proteins, which were restored by DA-8159 treatment. The proteins whose levels decreased >2-fold and attenuated by DA-8159 were determined alcohol dehydrogenase, aldolase A, annexin 1, and tropomyosin-rat, whereas proteins increased>2-fold and recovered by DA-8159 were found to be aldehyde dehydrogenase complex, guanine deaminase, creatine kinase-B, and phosphoglycerate mutase type B subunit.